U.S. patent application number 12/918740 was filed with the patent office on 2011-01-27 for pyrrolopyrimidinecarboxamides.
This patent application is currently assigned to NYCOMED GMBH. Invention is credited to Heiko Bernsmann, Jorg Diefenbach, Torsten Dunkern, Degenhard Marx, Beate Schmidt, Josef Stadlwieser, Alexander Sudau.
Application Number | 20110021479 12/918740 |
Document ID | / |
Family ID | 39855184 |
Filed Date | 2011-01-27 |
United States Patent
Application |
20110021479 |
Kind Code |
A1 |
Stadlwieser; Josef ; et
al. |
January 27, 2011 |
PYRROLOPYRIMIDINECARBOXAMIDES
Abstract
The compounds of Formula (I), ##STR00001## in which R1, R21,
R22, R23, R24, Y and R3 have the meanings as given in the
description, the salts thereof, the N-oxides of the compounds and
the salts thereof and the stereoisomers of the compounds, the
salts, the N-oxides of the compounds and the N-oxides of the salts
thereof are effective inhibitors of the type 5
phosphodiesterase.
Inventors: |
Stadlwieser; Josef;
(Konstanz, DE) ; Schmidt; Beate; (Allensbach,
DE) ; Bernsmann; Heiko; (Frankfurt, DE) ;
Sudau; Alexander; (Leichlingen, DE) ; Dunkern;
Torsten; (Volkertshausen, DE) ; Marx; Degenhard;
(Moos, DE) ; Diefenbach; Jorg;
(Stockach-Winterspuren, DE) |
Correspondence
Address: |
NATH & ASSOCIATES PLLC
112 South West Street
Alexandria
VA
22314
US
|
Assignee: |
NYCOMED GMBH
Konstanz
DE
|
Family ID: |
39855184 |
Appl. No.: |
12/918740 |
Filed: |
February 25, 2009 |
PCT Filed: |
February 25, 2009 |
PCT NO: |
PCT/EP09/52198 |
371 Date: |
August 20, 2010 |
Current U.S.
Class: |
514/171 ;
514/210.18; 514/234.2; 514/265.1; 544/117; 544/280 |
Current CPC
Class: |
A61P 1/16 20180101; A61P
11/00 20180101; C07D 487/04 20130101; A61P 19/00 20180101; A61P
11/06 20180101; A61P 43/00 20180101; A61P 9/08 20180101; A61P 15/00
20180101; A61P 9/12 20180101 |
Class at
Publication: |
514/171 ;
544/280; 514/265.1; 544/117; 514/234.2; 514/210.18 |
International
Class: |
A61K 31/573 20060101
A61K031/573; C07D 487/04 20060101 C07D487/04; A61K 31/519 20060101
A61K031/519; C07D 413/14 20060101 C07D413/14; A61K 31/5377 20060101
A61K031/5377; A61K 31/397 20060101 A61K031/397; A61P 11/00 20060101
A61P011/00; A61P 1/16 20060101 A61P001/16 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 27, 2008 |
EP |
08102052.1 |
Claims
1. Compound A compound of formula (I) ##STR00026## wherein R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, R11 is 1-4C-alkoxy or hydroxy, R21 is hydrogen,
R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy,
1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, or R21 and R22 combine to
form a group --O--CH.sub.2--O--, R23 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, or R22 and
R23 combine to form a group --O--CH.sub.2--O--, R24 is hydrogen, Y
is --(CH.sub.2).sub.n--, n is 0 or 1, R3 is a 4- to 7-membered
saturated heterocyclic ring containing one nitrogen atom and
optionally one oxygen atom, said heterocyclic ring being optionally
substituted by R4, or a 3-6C-cycloalkyl group substituted by R6, R4
is --C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, R41 is 1-4C-alkoxy or hydroxy, R42 is
1-4C-alkoxy or hydroxy, R43 is 1-4C-alkoxy or hydroxy, R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, R71 is
1-4C-alkoxy or hydroxy, R72 is 1-4C-alkoxy or hydroxy, R73 is
1-4C-alkoxy or hydroxy, R8 is hydrogen, R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, R91 is 1-4C-alkoxy or hydroxy, R92
is 1-4C-alkoxy or hydroxy, or a salt thereof, an N-oxide thereof, a
salt of an N-oxide thereof, a stereoisomer thereof or a salt of a
stereoisomer thereof.
2. The compound according to claim 1, wherein R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, R11 is 1-4C-alkoxy or hydroxy, R21 is hydrogen,
R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy,
1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, or R21 and R22 combine to
form a group --O--CH.sub.2--O--, R23 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, R24 is
hydrogen, Y is --(CH.sub.2).sub.n--, n is 0 or 1, R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, R41 is
1-4C-alkoxy or hydroxy, R42 is 1-4C-alkoxy or hydroxy, R43 is
1-4C-alkoxy or hydroxy, or a salt thereof, an N-oxide thereof, a
salt of an N-oxide thereof, a stereoisomer thereof or a salt of a
stereoisomer thereof.
3. The compound according to claim 1, wherein R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, R11 is 1-4C-alkoxy or hydroxy, R21 is hydrogen,
R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy,
1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, or R21 and R22 combine to
form a group --O--CH.sub.2--O--, R23 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, R24 is
hydrogen, Y is --(CH.sub.2).sub.n--, n is 0 or 1, R3 is a
cyclohexyl group substituted by R6, R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, R7 is hydrogen, 1-4C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, R71 is 1-4C-alkoxy or hydroxy, R72 is 1-4C-alkoxy or
hydroxy, R73 is 1-4C-alkoxy or hydroxy, R8 is hydrogen, R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, R91 is 1-4C-alkoxy or hydroxy, or a salt thereof,
an N-oxide thereof, a salt of an N-oxide thereof, a stereoisomer
thereof or a salt of a stereoisomer thereof.
4. The compound according to claim 1, wherein R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, R11 is 1-4C-alkoxy or hydroxy, R21 and R22
combine to form a group --O--CH.sub.2--O--, R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, R24
is hydrogen, Y is --(CH.sub.2).sub.n--, n is 0 or 1, R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, R41 is
1-4C-alkoxy or hydroxy, R42 is 1-4C-alkoxy or hydroxy, R43 is
1-4C-alkoxy or hydroxy, R6 is --NH--C(O)--R7, --C(O)--NR8R9 or
NH.sub.2, R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, R71 is 1-4C-alkoxy or hydroxy, R72 is 1-4C-alkoxy or
hydroxy, R73 is 1-4C-alkoxy or hydroxy, R8 is hydrogen, R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, R91 is 1-4C-alkoxy or hydroxy, or a salt thereof,
an N-oxide thereof, a salt of an N-oxide thereof, a stereoisomer
thereof or a salt of a stereoisomer thereof.
5. The compound according to claim 1 selected from the group
consisting of
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amid;
4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-formyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]-amide;
(R)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid ((S)-1-formyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-pyrrolidin-3-yl]-amide;
(S)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-formyl-piperidin-4-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-acetyl-piperidin-4-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-ylmethyl]-amide;
4-[({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidin-7-yl]-methanoyl}-amino)-methyl]-piperidine-1-carboxylic
acid ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-piperidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-propionyl-piperidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-acetyl)piperidin-3-ylmethyl]-amide;
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-piperidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-formyl-pyrrolidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-acetyl)-pyrrolidin-3-ylmethyl]-amide;
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (4-formyl-morpholin-2-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-propionyl-morpholin-2-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetyl)-morpholin-2-ylmethyl]-amide;
2-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-acetyl-azetidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-propionyl-azetidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-ethanoyl)-azetidin-3-yl]-amide;
3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-azetidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-piperidin-4-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-({1-[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
in-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amideter;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-propionylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-acetyl-piperidin-4-yl)-amide;
4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbony-
l]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-({1-[4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-(2-methoxy-acetyl)-pyrrolidin-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
bonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-formyl-piperidin-4-yl)-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-3-yl)-amide;
3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-(2-methoxy-acetyl)-piperidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-[4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]-
pyrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid ethyl
ester;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{(R)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{(S)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-ylmethyl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-acetyl)piperidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-acetyl)-pyrrolidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-hydroxy-acetyl)-morpholin-2-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionyl)-morpholin-2-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-azetidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)azetidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-((S)-2-hydroxy-propanoyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)pyrrolidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)pyrrolidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-pyrrolidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)pyrrolidin-3-yl]-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
(4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
(1-acetyl-piperidin-4-yl)-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-hydroxy-acetyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
[1-(2-hydroxy-acetyl)-piperidin-4-yl]-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide; and salts
thereof, N-oxides thereof, salts of the N-oxides thereof,
stereoisomers thereof and salts of the stereoisomers thereof.
6. (canceled)
7. (canceled)
8. A pharmaceutical composition comprising at least one of the
compounds, or pharmaceutically acceptable salts, N-oxides, salts of
the N-oxides, stereoisomers or salts of the stereoisomers thereof
according to claim 1, together with at least one pharmaceutically
acceptable auxiliary.
9. The pharmaceutical composition according to claim 8 further
comprising at least one therapeutic agent selected from the group
consisting of corticosteroids, anticholinergics, beta-mimetics,
lung surfactants, endothelin antagonists, prostacyclins, calcium
channel blockers, beta-blockers, type 4 phosphodiesterase
inhibitors, antidepressants and antibiotics.
10.-13. (canceled)
14. A method for treating or preventing an acute or chronic airway
disease comprising administering to a patient in need thereof a
therapeutically effective amount of a compound, or a
pharmaceutically acceptable salt, N-oxide, salt of an N-oxide,
stereoisomer or salt of a stereoisomer claim 1.
15. The method for treating or preventing an acute or chronic
airway disease according to claim 14, in which the acute or chronic
airway disease is selected from the group consisting of pulmonary
hypertension, lung fibrosis, asthma, bronchitis, emphysema and
chronic obstructive pulmonary disease.
16. A method of treating or preventing portal hypertension, liver
cirrhosis, toxic liver damage, hepatitis, non-alcoholic
steatohepatitis or liver fibrosis comprising administering to a
patient in need thereof a therapeutically effective amount of a
compound or a pharmaceutically acceptable salt, N-oxide, salt of an
N-oxide, stereoisomer or salt of a stereoisomer thereof according
to claim 1.
Description
FIELD OF APPLICATION OF THE INVENTION
[0001] The invention relates to pyrrolopyrimidinecarboxamide
compounds, processes for their preparation, pharmaceutical
compositions comprising said compounds and the use thereof in the
treatment or prophylaxis of diseases.
DESCRIPTION OF THE INVENTION
[0002] It has now been found that the pyrrolopyrimidinecarboxamide
compounds, which are described in detail below, have surprising and
advantageous properties.
[0003] The invention relates to compounds of formula (I)
##STR00002##
wherein [0004] R1 is --CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which
is optionally substituted by R11, [0005] R11 is 1-4C-alkoxy or
hydroxy, [0006] R21 is hydrogen, [0007] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [0008] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [0009] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [0010] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [0011] R24 is hydrogen,
[0012] Y is --(CH.sub.2).sub.n--, [0013] n is 0 or 1, [0014] R3 is
a 4- to 7-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0015] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0016] R41 is
1-4C-alkoxy or hydroxy, [0017] R42 is 1-4C-alkoxy or hydroxy,
[0018] R43 is 1-4C-alkoxy or hydroxy, [0019] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0020] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0021] R71 is 1-4C-alkoxy or hydroxy, [0022]
R72 is 1-4C-alkoxy or hydroxy, [0023] R73 is 1-4C-alkoxy or
hydroxy, [0024] R8 is hydrogen, [0025] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0026] R91 is 1-4C-alkoxy or
hydroxy, [0027] R92 is 1-4C-alkoxy or hydroxy, salts thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0028] 1-4C-Alkyl is a straight-chain or branched alkyl group
having 1 to 4 carbon atoms. Examples are methyl, ethyl, n-propyl,
iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl.
[0029] Halogen includes fluorine, chlorine, bromine and iodine. In
case of R22 and/or R23 being halogen, fluorine is preferred.
[0030] 3-6C-Cycloalkyl is a cycloalkyl group having 3 to 6 carbon
atoms, examples of which include the cyclopropyl, cyclobutyl,
cyclopentyl and cyclohexyl group. In case of R3 being
3-6C-cycloalkyl, cyclohexyl is preferred.
[0031] 1-4C-Alkoxy represents a group which, in addition to the
oxygen atom, contains a straight-chain or branched alkyl moiety
having 1 to 4 carbon atoms. Examples are methoxy, ethoxy,
n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy and
tert-butoxy.
[0032] 1-4C-Fluoroalkoxy represents a group which, in addition to
the oxygen atom, contains a straight-chain or branched alkyl moiety
having 1 to 4 carbon atoms, wherein one or more of the hydrogen
atoms of the alkyl moiety are replaced by fluorine. Examples
include, but are not limited to, a trifluoromethoxy,
difluoromethoxy, fluoromethoxy, perfluoroethoxy,
1,1,1-trifluoro-2-fluoroethoxy, 1,1,1-trifluoroethoxy,
1,1-difluoro-2,2-difluoroethoxy, 1,1-difluoro-2-fluoroethoxy,
1,1-difluoroethoxy, 1-fluoro-2,2-difluoroethoxy,
1-fluoro-2-fluoroethoxy, 1-fluoroethoxy, 2,2-difluoroethoxy,
2-fluoroethoxy, n-perfluoropropoxy, and n-perfluorobutoxy
group.
[0033] The group --C(O)-1-4C-alkyl represents a group which, in
addition to the carbonyl group --C(O)--, contains a straight-chain
or branched alkyl moiety having 1 to 4 carbon atoms. Examples are
methylcarbonyl, ethylcarbonyl, n-propylcarbonyl,
iso-propylcarbonyl, n-butylcarbonyl, iso-butylcarbonyl,
sec-butylcarbonyl and tert-butylcarbonyl.
[0034] The group --C(O)-3-6C-cycloalkyl represents a group which,
in addition to the carbonyl group --C(O)--, contains a cycloalkyl
group having 3 to 6 carbon atoms. Examples are cyclopropylcarbonyl,
cyclobutylcarbonyl, cyclopentylcarbonyl and cyclohexylcarbonyl.
[0035] The group --C(O)--O-1-4C-alkyl represents a group which, in
addition to the oxycarbonyl group --C(O)--O--, contains a
straight-chain or branched alkyl moiety having 1 to 4 carbon atoms.
Examples are methyloxycarbonyl, ethyloxycarbonyl,
n-propyloxycarbonyl, iso-propyloxycarbonyl, n-butyloxycarbonyl,
iso-butyloxycarbonyl, sec-butyloxycarbonyl and
tert-butyloxycarbonyl.
[0036] The 4- to 7-membered saturated heterocyclic ring containing
one nitrogen atom and optionally one oxygen atom includes, but is
not limited to, azetidinyl, oxazetidinyl, pyrrolidinyl,
oxazolidinyl, piperidinyl, morpholinyl, azepanyl and oxazepanyl, in
particular azetidinyl, 1,3-oxazetidinyl, pyrrolidinyl,
1,3-oxazolidinyl, piperidinyl, morpholinyl, azepanyl and
1,3-oxazepanyl, preferably azetidin-3-yl, pyrrolidin-3-yl,
morpholin-2-yl, piperidin-3-yl and piperidin-4-yl.
[0037] In a preferred embodiment, the invention relates to
compounds of formula (I), wherein [0038] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [0039] R11 is 1-4C-alkoxy or hydroxy, [0040]
R21 is hydrogen, [0041] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0042] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0043] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0044] R24 is hydrogen, [0045] Y is
--(CH.sub.2).sub.n--, [0046] n is 0 or 1, [0047] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, [0048] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0049] R41 is 1-4C-alkoxy or hydroxy, [0050]
R42 is 1-4C-alkoxy or hydroxy, [0051] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0052] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0053] R1 is
--CH.sub.2-3-4C-cycloalkyl, [0054] R21 is hydrogen, [0055] R22 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy,
1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [0056] or R21 and R22
combine to form a group --O--CH.sub.2--O--, [0057] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0058] or R22 and R23 combine to form a group --O--CH.sub.2--O--,
[0059] R24 is hydrogen, [0060] Y is --(CH.sub.2).sub.n--, [0061] n
is 0 or 1, [0062] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0063] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0064] R41 is 1-4C-alkoxy or hydroxy, [0065]
R42 is 1-4C-alkoxy or hydroxy, [0066] R43 is 1-4C-alkoxy or
hydroxy, [0067] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0068] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0069] R71 is
1-4C-alkoxy or hydroxy, [0070] R72 is 1-4C-alkoxy or hydroxy,
[0071] R73 is 1-4C-alkoxy or hydroxy, [0072] R8 is hydrogen, [0073]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, which is optionally substituted by R92, [0074] R91
is 1-4C-alkoxy or hydroxy, [0075] R92 is 1-4C-alkoxy or hydroxy, a
salt thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0076] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0077] R1 is 1-4C-alkyl which is
optionally substituted by R11, [0078] R11 is 1-4C-alkoxy or
hydroxy, [0079] R21 is hydrogen, [0080] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [0081] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [0082] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [0083] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [0084] R24 is hydrogen,
[0085] Y is --(CH.sub.2).sub.n--, [0086] n is 0 or 1, [0087] R3 is
a 4- to 7-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0088] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0089] R41 is
1-4C-alkoxy or hydroxy, [0090] R42 is 1-4C-alkoxy or hydroxy,
[0091] R43 is 1-4C-alkoxy or hydroxy, [0092] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0093] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0094] R71 is 1-4C-alkoxy or hydroxy, [0095]
R72 is 1-4C-alkoxy or hydroxy, [0096] R73 is 1-4C-alkoxy or
hydroxy, [0097] R8 is hydrogen, [0098] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0099] R91 is 1-4C-alkoxy or
hydroxy, [0100] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0101] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0102] R1 is 3-4C-alkyl which is
optionally substituted by R11, [0103] R11 is methoxy, [0104] R21 is
hydrogen, [0105] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [0106] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [0107] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0108] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0109] R24 is hydrogen, [0110] Y is
--(CH.sub.2).sub.n--, [0111] n is 0 or 1, [0112] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0113] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0114] R41 is
1-4C-alkoxy or hydroxy, [0115] R42 is 1-4C-alkoxy or hydroxy,
[0116] R43 is 1-4C-alkoxy or hydroxy, [0117] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0118] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0119] R71 is 1-4C-alkoxy or hydroxy, [0120]
R72 is 1-4C-alkoxy or hydroxy, [0121] R73 is 1-4C-alkoxy or
hydroxy, [0122] R8 is hydrogen, [0123] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0124] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0125] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0126] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0127] R11 is 1-4C-alkoxy or hydroxy, [0128]
R21 is hydrogen, [0129] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0130] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0131] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0132] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0133] R24 is hydrogen, [0134] Y is
--(CH.sub.2).sub.n--, [0135] n is 0 or 1, [0136] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[0137] R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl
group is optionally substituted by R41, --C(O)-3-6C-cycloalkyl,
wherein the 3-6C-cycloalkyl group is optionally substituted by R42,
or --C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0138] R41 is 1-4C-alkoxy or hydroxy, [0139]
R42 is 1-4C-alkoxy or hydroxy, [0140] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0141] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0142] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [0143] R11 is 1-4C-alkoxy or hydroxy, [0144]
R21 is hydrogen, [0145] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0146] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0147] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0148] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0149] R24 is hydrogen, [0150] Y is
--(CH.sub.2).sub.n--, [0151] n is 0 or 1, [0152] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being substituted by R4, [0153] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0154] R41 is 1-4C-alkoxy or hydroxy, [0155]
R42 is 1-4C-alkoxy or hydroxy, [0156] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0157] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0158] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [0159] R11 is 1-4C-alkoxy or hydroxy, [0160]
R21 is hydrogen, [0161] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0162] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0163] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0164] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0165] R24 is hydrogen, [0166] Y is
--(CH.sub.2).sub.n--, [0167] n is 0 or 1, [0168] R3 is a
3-6C-cycloalkyl group substituted by R6, [0169] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [0170] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0171] R71 is
1-4C-alkoxy or hydroxy, [0172] R72 is 1-4C-alkoxy or hydroxy,
[0173] R73 is 1-4C-alkoxy or hydroxy, [0174] R8 is hydrogen, [0175]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, which is optionally substituted by R92, [0176] R91
is 1-4C-alkoxy or hydroxy, [0177] R92 is 1-4C-alkoxy or hydroxy, a
salt thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0178] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0179] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [0180] R11 is 1-4C-alkoxy or hydroxy, [0181]
R21 is hydrogen, [0182] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0183] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0184] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0185] R24 is hydrogen, [0186] Y is
--(CH.sub.2).sub.n--, [0187] n is 0 or 1, [0188] R3 is a cyclohexyl
group substituted by R6, [0189] R6 is --NH--C(O)--R7, --C(O)--NR8R9
or NH.sub.2, [0190] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [0191] R71 is 1-4C-alkoxy or hydroxy, [0192] R72 is
1-4C-alkoxy or hydroxy, [0193] R73 is 1-4C-alkoxy or hydroxy,
[0194] R8 is hydrogen, [0195] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, which is optionally
substituted by R92, [0196] R91 is 1-4C-alkoxy or hydroxy, [0197]
R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[0198] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0199] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0200] R11 is 1-4C-alkoxy or hydroxy, [0201]
R21 is hydrogen, [0202] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0203] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0204] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0205] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0206] R24 is hydrogen, [0207] Y is
--(CH.sub.2).sub.n--, [0208] n is 0 or 1, [0209] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and one oxygen atom, said heterocyclic ring being optionally
substituted by R4, [0210] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0211] R41 is
1-4C-alkoxy or hydroxy, [0212] R42 is 1-4C-alkoxy or hydroxy,
[0213] R43 is 1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of
the compound or the salt thereof and a stereoisomer of the
compound, the salt, the N-oxide of the compound or the N-oxide of
the salt thereof.
[0214] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0215] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [0216] R11 is 1-4C-alkoxy, [0217] R21 is
hydrogen, [0218] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [0219] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [0220] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0221] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0222] R24 is hydrogen, [0223] Y is
--(CH.sub.2).sub.n--, [0224] n is 0 or 1, [0225] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and one oxygen atom, said heterocyclic ring being substituted by
R4, [0226] R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0227] R41 is
1-4C-alkoxy or hydroxy, [0228] R42 is 1-4C-alkoxy or hydroxy,
[0229] R43 is 1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of
the compound or the salt thereof and a stereoisomer of the
compound, the salt, the N-oxide of the compound or the N-oxide of
the salt thereof.
[0230] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0231] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0232] R11 is 1-4C-alkoxy or hydroxy, [0233]
R21 is hydrogen, [0234] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0235] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0236] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0237] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0238] R24 is hydrogen, [0239] Y is
--(CH.sub.2).sub.n--, [0240] n is 0 or 1, [0241] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being substituted by R4, [0242] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0243] R41 is 1-4C-alkoxy or hydroxy, [0244]
R42 is 1-4C-alkoxy or hydroxy, [0245] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0246] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0247] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0248] R11 is 1-4C-alkoxy or hydroxy, [0249]
R21 is hydrogen, [0250] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0251] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0252] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0253] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0254] R24 is hydrogen, [0255] Y is
--(CH.sub.2).sub.n--, [0256] n is 0 or 1, [0257] R3 is a 5-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being substituted by R4, [0258] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0259] R41 is 1-4C-alkoxy or hydroxy, [0260]
R42 is 1-4C-alkoxy or hydroxy, [0261] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0262] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0263] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0264] R11 is 1-4C-alkoxy or hydroxy, [0265]
R21 is hydrogen, [0266] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0267] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0268] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0269] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0270] R24 is hydrogen, [0271] Y is
--(CH.sub.2).sub.n--, [0272] n is 0 or 1, [0273] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being substituted by R4, [0274] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0275] R41 is 1-4C-alkoxy or hydroxy, [0276]
R42 is 1-4C-alkoxy or hydroxy, [0277] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0278] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0279] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0280] R11 is 1-4C-alkoxy, [0281] R21 is
hydrogen, [0282] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [0283] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [0284] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0285] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0286] R24 is hydrogen, [0287] Y is
--(CH.sub.2).sub.n--, [0288] n is 0 or 1, [0289] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom and one
oxygen atom, said heterocyclic ring being substituted by R4, [0290]
R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0291] R41 is 1-4C-alkoxy or hydroxy, [0292]
R42 is 1-4C-alkoxy or hydroxy, [0293] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0294] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0295] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0296] R11 is 1-4C-alkoxy or hydroxy, [0297]
R21 is hydrogen, [0298] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or --C(O)-1-4C-alkyl, [0299] or R21 and R22
combine to form a group --O--CH.sub.2--O--, [0300] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy or hydroxy, [0301] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [0302] R24 is hydrogen,
[0303] Y is --(CH.sub.2).sub.n--, [0304] n is 0 or 1, [0305] R3 is
a 3-6C-cycloalkyl group substituted by R6, [0306] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [0307] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0308] R71 is
1-4C-alkoxy or hydroxy, [0309] R72 is 1-4C-alkoxy or hydroxy,
[0310] R73 is 1-4C-alkoxy or hydroxy, [0311] R8 is hydrogen, [0312]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, which is optionally substituted by R92, [0313] R91
is 1-4C-alkoxy or hydroxy, [0314] R92 is 1-4C-alkoxy or hydroxy, a
salt thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0315] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0316] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0317] R11 is 1-4C-alkoxy or hydroxy, [0318]
R21 is hydrogen, [0319] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or --C(O)-1-4C-alkyl, [0320] or R21 and R22
combine to form a group --O--CH.sub.2--O--, [0321] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy or hydroxy, [0322] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [0323] R24 is hydrogen,
[0324] Y is --(CH.sub.2).sub.n--, [0325] n is 0 or 1, [0326] R3 is
a cyclohexyl group substituted by R6, [0327] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0328] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0329] R71 is 1-4C-alkoxy or hydroxy, [0330]
R72 is 1-4C-alkoxy or hydroxy, [0331] R73 is 1-4C-alkoxy or
hydroxy, [0332] R8 is hydrogen, [0333] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0334] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0335] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0336] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0337] R11 is 1-4C-alkoxy or hydroxy, [0338]
R21 is hydrogen, [0339] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0340] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0341] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0342] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0343] R24 is hydrogen, [0344] Y is
--(CH.sub.2).sub.n--, [0345] n is 0, [0346] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0347] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0348] R41 is
1-4C-alkoxy or hydroxy, [0349] R42 is 1-4C-alkoxy or hydroxy,
[0350] R43 is 1-4C-alkoxy or hydroxy, [0351] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0352] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0353] R71 is 1-4C-alkoxy or hydroxy, [0354]
R72 is 1-4C-alkoxy or hydroxy, [0355] R73 is 1-4C-alkoxy or
hydroxy, [0356] R8 is hydrogen, [0357] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0358] R91 is 1-4C-alkoxy or
hydroxy, [0359] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0360] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0361] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0362] R11 is 1-4C-alkoxy or hydroxy, [0363]
R21 is hydrogen, [0364] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0365] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0366] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0367] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0368] R24 is hydrogen, [0369] Y is
--(CH.sub.2).sub.n--, [0370] n is 1, [0371] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0372] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0373] R41 is
1-4C-alkoxy or hydroxy, [0374] R42 is 1-4C-alkoxy or hydroxy,
[0375] R43 is 1-4C-alkoxy or hydroxy, [0376] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0377] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0378] R71 is 1-4C-alkoxy or hydroxy, [0379]
R72 is 1-4C-alkoxy or hydroxy, [0380] R73 is 1-4C-alkoxy or
hydroxy, [0381] R8 is hydrogen, [0382] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0383] R91 is 1-4C-alkoxy or
hydroxy, [0384] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0385] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0386] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0387] R11 is 1-4C-alkoxy or hydroxy, [0388]
R21 is hydrogen, [0389] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0390] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0391] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0392] R24 is hydrogen, [0393] Y is
--(CH.sub.2).sub.n--, [0394] n is 0 or 1, [0395] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0396] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0397] R41 is
1-4C-alkoxy or hydroxy, [0398] R42 is 1-4C-alkoxy or hydroxy,
[0399] R43 is 1-4C-alkoxy or hydroxy, [0400] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0401] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0402] R71 is 1-4C-alkoxy or hydroxy, [0403]
R72 is 1-4C-alkoxy or hydroxy, [0404] R73 is 1-4C-alkoxy or
hydroxy, [0405] R8 is hydrogen, [0406] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0407] R91 is 1-4C-alkoxy or
hydroxy, [0408] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0409] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0410] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0411] R11 is 1-4C-alkoxy or hydroxy, [0412]
R21 and R22 combine to form a group --O--CH.sub.2--O--, [0413] R23
is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0414] R24 is hydrogen, [0415] Y is
--(CH.sub.2).sub.n--, [0416] n is 0 or 1, [0417] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0418] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0419] R41 is
1-4C-alkoxy or hydroxy, [0420] R42 is 1-4C-alkoxy or hydroxy,
[0421] R43 is 1-4C-alkoxy or hydroxy, [0422] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0423] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0424] R71 is 1-4C-alkoxy or hydroxy, [0425]
R72 is 1-4C-alkoxy or hydroxy, [0426] R73 is 1-4C-alkoxy or
hydroxy, [0427] R8 is hydrogen, [0428] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0429] R91 is 1-4C-alkoxy or
hydroxy, [0430] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0431] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0432] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0433] R11 is 1-4C-alkoxy or hydroxy, [0434]
R21, R22, R23 and R24 are each hydrogen, [0435] Y is
--(CH.sub.2).sub.n--, [0436] n is 0 or 1, [0437] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0438] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0439] R41 is
1-4C-alkoxy or hydroxy, [0440] R42 is 1-4C-alkoxy or hydroxy,
[0441] R43 is 1-4C-alkoxy or hydroxy, [0442] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0443] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0444] R71 is 1-4C-alkoxy or hydroxy, [0445]
R72 is 1-4C-alkoxy or hydroxy, [0446] R73 is 1-4C-alkoxy or
hydroxy, [0447] R8 is hydrogen, [0448] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0449] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0450] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0451] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0452] R11 is 1-4C-alkoxy or hydroxy, [0453]
R21 is hydrogen, [0454] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0455] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0456] R23 is 1-4C-alkoxy, [0457] R24 is hydrogen, [0458] Y is
--(CH.sub.2).sub.n--, [0459] n is 0 or 1, [0460] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0461] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0462] R41 is
1-4C-alkoxy or hydroxy, [0463] R42 is 1-4C-alkoxy or hydroxy,
[0464] R43 is 1-4C-alkoxy or hydroxy, [0465] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0466] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0467] R71 is 1-4C-alkoxy or hydroxy, [0468]
R72 is 1-4C-alkoxy or hydroxy, [0469] R73 is 1-4C-alkoxy or
hydroxy, [0470] R8 is hydrogen, [0471] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0472] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0473] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0474] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0475] R11 is 1-4C-alkoxy or hydroxy, [0476]
R21 is hydrogen, [0477] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0478] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0479] R23 is hydroxy, [0480] R24 is hydrogen, [0481] Y is
--(CH.sub.2).sub.n--, [0482] n is 0 or 1, [0483] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0484] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0485] R41 is
1-4C-alkoxy or hydroxy, [0486] R42 is 1-4C-alkoxy or hydroxy,
[0487] R43 is 1-4C-alkoxy or hydroxy, [0488] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0489] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0490] R71 is 1-4C-alkoxy or hydroxy, [0491]
R72 is 1-4C-alkoxy or hydroxy, [0492] R73 is 1-4C-alkoxy or
hydroxy, [0493] R8 is hydrogen, [0494] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0495] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0496] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0497] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0498] R11 is 1-4C-alkoxy or hydroxy, [0499]
R21 is hydrogen, [0500] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0501] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0502] R23 is 1-4C-fluoroalkoxy, [0503] R24 is hydrogen, [0504] Y
is --(CH.sub.2).sub.n--, [0505] n is 0 or 1, [0506] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0507] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0508] R41 is
1-4C-alkoxy or hydroxy, [0509] R42 is 1-4C-alkoxy or hydroxy,
[0510] R43 is 1-4C-alkoxy or hydroxy, [0511] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0512] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0513] R71 is 1-4C-alkoxy or hydroxy, [0514]
R72 is 1-4C-alkoxy or hydroxy, [0515] R73 is 1-4C-alkoxy or
hydroxy, [0516] R8 is hydrogen, [0517] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0518] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0519] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0520] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0521] R11 is 1-4C-alkoxy or hydroxy, [0522]
R21 is hydrogen, [0523] R22 is halogen, [0524] R23 is 1-4C-alkoxy,
[0525] R24 is hydrogen, [0526] Y is --(CH.sub.2).sub.n--, [0527] n
is 0 or 1, [0528] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0529] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0530] R41 is 1-4C-alkoxy or hydroxy, [0531]
R42 is 1-4C-alkoxy or hydroxy, [0532] R43 is 1-4C-alkoxy or
hydroxy, [0533] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0534] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0535] R71 is
1-4C-alkoxy or hydroxy, [0536] R72 is 1-4C-alkoxy or hydroxy,
[0537] R73 is 1-4C-alkoxy or hydroxy, [0538] R8 is hydrogen, [0539]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0540] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0541] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0542] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0543] R11 is 1-4C-alkoxy or hydroxy, [0544]
R21 is hydrogen, [0545] R22 is --C(O)-1-4C-alkyl, [0546] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0547] R24 is hydrogen, [0548] Y is
--(CH.sub.2).sub.n--, [0549] n is 0 or 1, [0550] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0551] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0552] R41 is
1-4C-alkoxy or hydroxy, [0553] R42 is 1-4C-alkoxy or hydroxy,
[0554] R43 is 1-4C-alkoxy or hydroxy, [0555] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0556] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0557] R71 is 1-4C-alkoxy or hydroxy, [0558]
R72 is 1-4C-alkoxy or hydroxy, [0559] R73 is 1-4C-alkoxy or
hydroxy, [0560] R8 is hydrogen, [0561] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0562] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0563] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0564] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0565] R11 is 1-4C-alkoxy or hydroxy, [0566]
R21 is hydrogen, [0567] R22 is halogen, [0568] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0569] R24 is hydrogen, [0570] Y is --(CH.sub.2).sub.n--, [0571] n
is 0 or 1, [0572] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0573] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0574] R41 is 1-4C-alkoxy or hydroxy, [0575]
R42 is 1-4C-alkoxy or hydroxy, [0576] R43 is 1-4C-alkoxy or
hydroxy, [0577] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0578] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0579] R71 is
1-4C-alkoxy or hydroxy, [0580] R72 is 1-4C-alkoxy or hydroxy,
[0581] R73 is 1-4C-alkoxy or hydroxy, [0582] R8 is hydrogen, [0583]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0584] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0585] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0586] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0587] R11 is 1-4C-alkoxy or hydroxy, [0588]
R21 is hydrogen, [0589] R22 is 1-4C-alkoxy, [0590] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0591] R24 is hydrogen, [0592] Y is --(CH.sub.2).sub.n--, [0593] n
is 0 or 1, [0594] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0595] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0596] R41 is 1-4C-alkoxy or hydroxy, [0597]
R42 is 1-4C-alkoxy or hydroxy, [0598] R43 is 1-4C-alkoxy or
hydroxy, [0599] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0600] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0601] R71 is
1-4C-alkoxy or hydroxy, [0602] R72 is 1-4C-alkoxy or hydroxy,
[0603] R73 is 1-4C-alkoxy or hydroxy, [0604] R8 is hydrogen, [0605]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0606] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0607] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0608] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0609] R11 is 1-4C-alkoxy or hydroxy, [0610]
R21 is hydrogen, [0611] R22 is hydroxy, [0612] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0613] R24 is hydrogen, [0614] Y is --(CH.sub.2).sub.n--, [0615] n
is 0 or 1, [0616] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0617] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0618] R41 is 1-4C-alkoxy or hydroxy, [0619]
R42 is 1-4C-alkoxy or hydroxy, [0620] R43 is 1-4C-alkoxy or
hydroxy, [0621] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0622] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0623] R71 is
1-4C-alkoxy or hydroxy, [0624] R72 is 1-4C-alkoxy or hydroxy,
[0625] R73 is 1-4C-alkoxy or hydroxy, [0626] R8 is hydrogen, [0627]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0628] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0629] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0630] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0631] R11 is 1-4C-alkoxy or hydroxy, [0632]
R21 is hydrogen, [0633] R22 is 1-4C-fluoroalkoxy, [0634] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0635] R24 is hydrogen, [0636] Y is
--(CH.sub.2).sub.n--, [0637] n is 0 or 1, [0638] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0639] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0640] R41 is
1-4C-alkoxy or hydroxy, [0641] R42 is 1-4C-alkoxy or hydroxy,
[0642] R43 is 1-4C-alkoxy or hydroxy, [0643] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0644] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0645] R71 is 1-4C-alkoxy or hydroxy, [0646]
R72 is 1-4C-alkoxy or hydroxy, [0647] R73 is 1-4C-alkoxy or
hydroxy, [0648] R8 is hydrogen, [0649] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0650] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0651] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0652] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0653] R11 is 1-4C-alkoxy or hydroxy, [0654]
R21 is hydrogen, [0655] R22 is 1-4C-alkoxy, [0656] R23 is halogen,
[0657] R24 is hydrogen, [0658] Y is --(CH.sub.2).sub.n--, [0659] n
is 0 or 1, [0660] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0661] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0662] R41 is 1-4C-alkoxy or hydroxy, [0663]
R42 is 1-4C-alkoxy or hydroxy, [0664] R43 is 1-4C-alkoxy or
hydroxy, [0665] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0666] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0667] R71 is
1-4C-alkoxy or hydroxy, [0668] R72 is 1-4C-alkoxy or hydroxy,
[0669] R73 is 1-4C-alkoxy or hydroxy, [0670] R8 is hydrogen, [0671]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0672] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0673] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0674] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0675] R11 is 1-4C-alkoxy or hydroxy, [0676]
R21 is hydrogen, [0677] R22 is 1-4C-alkyl, [0678] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0679] R24 is hydrogen, [0680] Y is --(CH.sub.2).sub.n--, [0681] n
is 0 or 1, [0682] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0683] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0684] R41 is 1-4C-alkoxy or hydroxy, [0685]
R42 is 1-4C-alkoxy or hydroxy, [0686] R43 is 1-4C-alkoxy or
hydroxy, [0687] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0688] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0689] R71 is
1-4C-alkoxy or hydroxy, [0690] R72 is 1-4C-alkoxy or hydroxy,
[0691] R73 is 1-4C-alkoxy or hydroxy, [0692] R8 is hydrogen, [0693]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0694] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0695] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0696] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0697] R11 is 1-4C-alkoxy or hydroxy, [0698]
R21 and R22 combine to form a group --O--CH.sub.2--O--, [0699] R23
is hydrogen, [0700] R24 is hydrogen, [0701] Y is
--(CH.sub.2).sub.n--, [0702] n is 0 or 1, [0703] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0704] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0705] R41 is
1-4C-alkoxy or hydroxy, [0706] R42 is 1-4C-alkoxy or hydroxy,
[0707] R43 is 1-4C-alkoxy or hydroxy, [0708] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0709] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0710] R71 is 1-4C-alkoxy or hydroxy, [0711]
R72 is 1-4C-alkoxy or hydroxy, [0712] R73 is 1-4C-alkoxy or
hydroxy, [0713] R8 is hydrogen, [0714] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [0715] R91 is 1-4C-alkoxy or
hydroxy, [0716] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[0717] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0718] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0719] R11 is 1-4C-alkoxy or hydroxy, [0720]
R21 is hydrogen, [0721] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0722] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0723] R23 is halogen, [0724] R24 is hydrogen, [0725] Y is
--(CH.sub.2).sub.n--, [0726] n is 0 or 1, [0727] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0728] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0729] R41 is
1-4C-alkoxy or hydroxy, [0730] R42 is 1-4C-alkoxy or hydroxy,
[0731] R43 is 1-4C-alkoxy or hydroxy, [0732] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0733] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0734] R71 is 1-4C-alkoxy or hydroxy, [0735]
R72 is 1-4C-alkoxy or hydroxy, [0736] R73 is 1-4C-alkoxy or
hydroxy, [0737] R8 is hydrogen, [0738] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0739] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0740] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0741] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0742] R11 is 1-4C-alkoxy or hydroxy, [0743]
R21 is hydrogen, [0744] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0745] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0746] R23 and R24 are hydrogen, [0747] Y is --(CH.sub.2).sub.n--,
[0748] n is 0 or 1, [0749] R3 is a 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom, said heterocyclic ring being optionally substituted by
R4, or a 3-6C-cycloalkyl group substituted by R6, [0750] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0751] R41 is 1-4C-alkoxy or hydroxy, [0752]
R42 is 1-4C-alkoxy or hydroxy, [0753] R43 is 1-4C-alkoxy or
hydroxy, [0754] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0755] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0756] R71 is
1-4C-alkoxy or hydroxy, [0757] R72 is 1-4C-alkoxy or hydroxy,
[0758] R73 is 1-4C-alkoxy or hydroxy, [0759] R8 is hydrogen, [0760]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0761] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0762] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0763] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0764] R11 is 1-4C-alkoxy or hydroxy, [0765]
R21 is hydrogen, [0766] R22 is fluorine, [0767] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0768] R24 is hydrogen, [0769] Y is --(CH.sub.2).sub.n--, [0770] n
is 0 or 1, [0771] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0772] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0773] R41 is 1-4C-alkoxy or hydroxy, [0774]
R42 is 1-4C-alkoxy or hydroxy, [0775] R43 is 1-4C-alkoxy or
hydroxy, [0776] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0777] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0778] R71 is
1-4C-alkoxy or hydroxy, [0779] R72 is 1-4C-alkoxy or hydroxy,
[0780] R73 is 1-4C-alkoxy or hydroxy, [0781] R8 is hydrogen, [0782]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0783] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0784] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0785] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0786] R11 is 1-4C-alkoxy or hydroxy, [0787]
R21 is hydrogen, [0788] R22 is methoxy, [0789] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0790] R24 is hydrogen, [0791] Y is --(CH.sub.2).sub.n--, [0792] n
is 0 or 1, [0793] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0794] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0795] R41 is 1-4C-alkoxy or hydroxy, [0796]
R42 is 1-4C-alkoxy or hydroxy, [0797] R43 is 1-4C-alkoxy or
hydroxy, [0798] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0799] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0800] R71 is
1-4C-alkoxy or hydroxy, [0801] R72 is 1-4C-alkoxy or hydroxy,
[0802] R73 is 1-4C-alkoxy or hydroxy, [0803] R8 is hydrogen, [0804]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0805] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0806] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0807] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0808] R11 is 1-4C-alkoxy or hydroxy, [0809]
R21 is hydrogen, [0810] R22 is methyl, [0811] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[0812] R24 is hydrogen, [0813] Y is --(CH.sub.2).sub.n--, [0814] n
is 0 or 1, [0815] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0816] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0817] R41 is 1-4C-alkoxy or hydroxy, [0818]
R42 is 1-4C-alkoxy or hydroxy, [0819] R43 is 1-4C-alkoxy or
hydroxy, [0820] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0821] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0822] R71 is
1-4C-alkoxy or hydroxy, [0823] R72 is 1-4C-alkoxy or hydroxy,
[0824] R73 is 1-4C-alkoxy or hydroxy, [0825] R8 is hydrogen, [0826]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0827] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0828] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0829] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0830] R11 is 1-4C-alkoxy or hydroxy, [0831]
R21 is hydrogen, [0832] R22 is methylcarbonyl, [0833] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [0834] R24 is hydrogen, [0835] Y is
--(CH.sub.2).sub.n--, [0836] n is 0 or 1, [0837] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0838] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0839] R41 is
1-4C-alkoxy or hydroxy, [0840] R42 is 1-4C-alkoxy or hydroxy,
[0841] R43 is 1-4C-alkoxy or hydroxy, [0842] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0843] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0844] R71 is 1-4C-alkoxy or hydroxy, [0845]
R72 is 1-4C-alkoxy or hydroxy, [0846] R73 is 1-4C-alkoxy or
hydroxy, [0847] R8 is hydrogen, [0848] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0849] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0850] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0851] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0852] R11 is 1-4C-alkoxy or hydroxy, [0853]
R21 is hydrogen, [0854] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0855] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0856] R23 is fluorine, [0857] R24 is hydrogen, [0858] Y is
--(CH.sub.2).sub.n--, [0859] n is 0 or 1, [0860] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0861] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0862] R41 is
1-4C-alkoxy or hydroxy, [0863] R42 is 1-4C-alkoxy or hydroxy,
[0864] R43 is 1-4C-alkoxy or hydroxy, [0865] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0866] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0867] R71 is 1-4C-alkoxy or hydroxy, [0868]
R72 is 1-4C-alkoxy or hydroxy, [0869] R73 is 1-4C-alkoxy or
hydroxy, [0870] R8 is hydrogen, [0871] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0872] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0873] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0874] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0875] R11 is 1-4C-alkoxy or hydroxy, [0876]
R21 is hydrogen, [0877] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0878] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0879] R23 is methoxy, [0880] R24 is hydrogen, [0881] Y is
--(CH.sub.2).sub.n--, [0882] n is 0 or 1, [0883] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0884] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [0885] R41 is
1-4C-alkoxy or hydroxy, [0886] R42 is 1-4C-alkoxy or hydroxy,
[0887] R43 is 1-4C-alkoxy or hydroxy, [0888] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0889] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [0890] R71 is 1-4C-alkoxy or hydroxy, [0891]
R72 is 1-4C-alkoxy or hydroxy, [0892] R73 is 1-4C-alkoxy or
hydroxy, [0893] R8 is hydrogen, [0894] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [0895] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[0896] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0897] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0898] R11 is 1-4C-alkoxy or hydroxy, [0899]
R21 is hydrogen, [0900] R22 is methoxy, [0901] R23 is fluorine,
[0902] R24 is hydrogen, [0903] Y is --(CH.sub.2).sub.n--, [0904] n
is 0 or 1, [0905] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0906] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0907] R41 is 1-4C-alkoxy or hydroxy, [0908]
R42 is 1-4C-alkoxy or hydroxy, [0909] R43 is 1-4C-alkoxy or
hydroxy, [0910] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0911] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0912] R71 is
1-4C-alkoxy or hydroxy, [0913] R72 is 1-4C-alkoxy or hydroxy,
[0914] R73 is 1-4C-alkoxy or hydroxy, [0915] R8 is hydrogen, [0916]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0917] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0918] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0919] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0920] R11 is 1-4C-alkoxy or hydroxy, [0921]
R21 is hydrogen, [0922] R22 is fluorine, [0923] R23 is methoxy,
[0924] R24 is hydrogen, [0925] Y is --(CH.sub.2).sub.n--, [0926] n
is 0 or 1, [0927] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [0928] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [0929] R41 is 1-4C-alkoxy or hydroxy, [0930]
R42 is 1-4C-alkoxy or hydroxy, [0931] R43 is 1-4C-alkoxy or
hydroxy, [0932] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[0933] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0934] R71 is
1-4C-alkoxy or hydroxy, [0935] R72 is 1-4C-alkoxy or hydroxy,
[0936] R73 is 1-4C-alkoxy or hydroxy, [0937] R8 is hydrogen, [0938]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0939] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0940] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0941] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0942] R11 is 1-4C-alkoxy or hydroxy, [0943]
R21 is hydrogen, [0944] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0945] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0946] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0947] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0948] R24 is hydrogen, [0949] Y is
--(CH.sub.2).sub.n--, [0950] n is 0 or 1, [0951] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0952] R4 is --C(O)--H, [0953] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [0954] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [0955] R71 is
1-4C-alkoxy or hydroxy, [0956] R72 is 1-4C-alkoxy or hydroxy,
[0957] R73 is 1-4C-alkoxy or hydroxy, [0958] R8 is hydrogen, [0959]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [0960] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[0961] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0962] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0963] R11 is 1-4C-alkoxy or hydroxy, [0964]
R21 is hydrogen, [0965] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0966] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0967] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0968] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0969] R24 is hydrogen, [0970] Y is
--(CH.sub.2).sub.n--, [0971] n is 0 or 1, [0972] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0973] R4 is --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41, [0974] R41 is
1-4C-alkoxy or hydroxy, [0975] R6 is --NH--C(O)--R7, --C(O)--NR8R9
or NH.sub.2, [0976] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [0977] R71 is 1-4C-alkoxy or hydroxy, [0978] R72 is
1-4C-alkoxy or hydroxy, [0979] R73 is 1-4C-alkoxy or hydroxy,
[0980] R8 is hydrogen, [0981] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [0982] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[0983] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [0984] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [0985] R11 is 1-4C-alkoxy or hydroxy, [0986]
R21 is hydrogen, [0987] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[0988] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[0989] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [0990] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [0991] R24 is hydrogen, [0992] Y is
--(CH.sub.2).sub.n--, [0993] n is 0 or 1, [0994] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [0995] R4 is --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by [0996] R42,
[0997] R42 is 1-4C-alkoxy or hydroxy, [0998] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [0999] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [1000] R71 is 1-4C-alkoxy or hydroxy, [1001]
R72 is 1-4C-alkoxy or hydroxy, [1002] R73 is 1-4C-alkoxy or
hydroxy, [1003] R8 is hydrogen, [1004] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [1005] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[1006] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1007] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1008] R11 is 1-4C-alkoxy or hydroxy, [1009]
R21 is hydrogen, [1010] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1011] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1012] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1013] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1014] R24 is hydrogen, [1015] Y is
--(CH.sub.2).sub.n--, [1016] n is 0 or 1, [1017] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1018] R4 is --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1019] R43 is
1-4C-alkoxy or hydroxy, [1020] R6 is --NH--C(O)--R7, --C(O)--NR8R9
or NH.sub.2, [1021] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [1022] R71 is 1-4C-alkoxy or hydroxy, [1023] R72 is
1-4C-alkoxy or hydroxy, [1024] R73 is 1-4C-alkoxy or hydroxy,
[1025] R8 is hydrogen, [1026] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [1027] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1028] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1029] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1030] R11 is 1-4C-alkoxy or hydroxy, [1031]
R21 is hydrogen, [1032] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1033] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1034] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1035] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1036] R24 is hydrogen, [1037] Y is
--(CH.sub.2).sub.n--, [1038] n is 0 or 1, [1039] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1040] R4 is --C(O)--O-1-4C-alkyl, [1041] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1042] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1043] R71 is
1-4C-alkoxy or hydroxy, [1044] R72 is 1-4C-alkoxy or hydroxy,
[1045] R73 is 1-4C-alkoxy or hydroxy, [1046] R8 is hydrogen, [1047]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1048] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1049] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1050] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1051] R11 is 1-4C-alkoxy or hydroxy, [1052]
R21 is hydrogen, [1053] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1054] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1055] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1056] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1057] R24 is hydrogen, [1058] Y is
--(CH.sub.2).sub.n--, [1059] n is 0 or 1, [1060] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1061] R4 is --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41, [1062] R41 is
1-4C-alkoxy, [1063] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or
NH.sub.2, [1064] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [1065] R71 is 1-4C-alkoxy or hydroxy, [1066] R72 is
1-4C-alkoxy or hydroxy, [1067] R73 is 1-4C-alkoxy or hydroxy,
[1068] R8 is hydrogen, [1069] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [1070] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1071] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1072] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1073] R11 is 1-4C-alkoxy or hydroxy, [1074]
R21 is hydrogen, [1075] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1076] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1077] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1078] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1079] R24 is hydrogen, [1080] Y is
--(CH.sub.2).sub.n--, [1081] n is 0 or 1, [1082] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1083] R4 is --C(O)-2-4C-alkyl, wherein the
2-4C-alkyl group is optionally substituted by R41, [1084] R41 is
methoxy, [1085] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or [1086] R7 is
hydrogen, 1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1087] R71 is
1-4C-alkoxy or hydroxy, [1088] R72 is 1-4C-alkoxy or hydroxy,
[1089] R73 is 1-4C-alkoxy or hydroxy, [1090] R8 is hydrogen, [1091]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1092] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1093] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1094] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1095] R11 is 1-4C-alkoxy or hydroxy, [1096]
R21 is hydrogen, [1097] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1098] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1099] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1100] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1101] R24 is hydrogen, [1102] Y is
--(CH.sub.2).sub.n--, [1103] n is 0 or 1, [1104] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1105] R4 is --C(O)-2-4C-alkyl, wherein the
2-4C-alkyl group is optionally substituted by R41, [1106] R41 is
hydroxy, [1107] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[1108] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1109] R71 is
1-4C-alkoxy or hydroxy, [1110] R72 is 1-4C-alkoxy or hydroxy,
[1111] R73 is 1-4C-alkoxy or hydroxy, [1112] R8 is hydrogen, [1113]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1114] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1115] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1116] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1117] R11 is 1-4C-alkoxy or hydroxy, [1118]
R21 is hydrogen, [1119] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1120] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1121] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1122] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1123] R24 is hydrogen, [1124] Y is
--(CH.sub.2).sub.n--, [1125] n is 0 or 1, [1126] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1127] R4 is --C(O)-cyclopropyl, wherein the
cyclopropyl group is optionally substituted by R42, [1128] R42 is
1-4C-alkoxy, [1129] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or
NH.sub.2, [1130] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [1131] R71 is 1-4C-alkoxy or hydroxy, [1132] R72 is
1-4C-alkoxy or hydroxy, [1133] R73 is 1-4C-alkoxy or hydroxy,
[1134] R8 is hydrogen, [1135] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [1136] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1137] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1138] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1139] R11 is 1-4C-alkoxy or hydroxy, [1140]
R21 is hydrogen, [1141] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1142] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1143] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1144] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1145] R24 is hydrogen, [1146] Y is
--(CH.sub.2).sub.n--, [1147] n is 0 or 1, [1148] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1149] R4 is --C(O)-cyclopropyl, wherein the
cyclopropyl group is optionally substituted by R42, [1150] R42 is
methoxy, [1151] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[1152] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1153] R71 is
1-4C-alkoxy or hydroxy, [1154] R72 is 1-4C-alkoxy or hydroxy,
[1155] R73 is 1-4C-alkoxy or hydroxy, [1156] R8 is hydrogen, [1157]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1158] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1159] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1160] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1161] R11 is 1-4C-alkoxy or hydroxy, [1162]
R21 is hydrogen, [1163] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1164] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1165] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1166] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1167] R24 is hydrogen, [1168] Y is
--(CH.sub.2).sub.n--, [1169] n is 0 or 1, [1170] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1171] R4 is --C(O)-cyclopropyl, wherein the
cyclopropyl group is optionally substituted by R42, [1172] R42 is
hydroxy, [1173] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[1174] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1175] R71 is
1-4C-alkoxy or hydroxy, [1176] R72 is 1-4C-alkoxy or hydroxy,
[1177] R73 is 1-4C-alkoxy or hydroxy, [1178] R8 is hydrogen, [1179]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1180] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, to the salt, the N-oxide of the
compound or the N-oxide of the salt thereof.
[1181] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1182] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1183] R11 is 1-4C-alkoxy or hydroxy, [1184]
R21 is hydrogen, [1185] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1186] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1187] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1188] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1189] R24 is hydrogen, [1190] Y is
--(CH.sub.2).sub.n--, [1191] n is 0 or 1, [1192] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1193] R4 --C(O)--O-1-4C-alkyl, which is
optionally substituted by R43, [1194] R43 is 1-2C-alkoxy, [1195] R6
is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1196] R7 is
hydrogen, 1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1197] R71 is
1-4C-alkoxy or hydroxy, [1198] R72 is 1-4C-alkoxy or hydroxy,
[1199] R73 is 1-4C-alkoxy or hydroxy, [1200] R8 is hydrogen, [1201]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1202] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1203] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1204] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1205] R11 is 1-4C-alkoxy or hydroxy, [1206]
R21 is hydrogen, [1207] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1208] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1209] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1210] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1211] R24 is hydrogen, [1212] Y is
--(CH.sub.2).sub.n--, [1213] n is 0 or 1, [1214] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1215] R4 --C(O)--O-1-4C-alkyl, which is
optionally substituted by R43, [1216] R43 is methoxy, [1217] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1218] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1219] R71 is
1-4C-alkoxy or hydroxy, [1220] R72 is 1-4C-alkoxy or hydroxy,
[1221] R73 is 1-4C-alkoxy or hydroxy, [1222] R8 is hydrogen, [1223]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1224] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1225] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1226] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1227] R11 is 1-4C-alkoxy or hydroxy, [1228]
R21 is hydrogen, [1229] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1230] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1231] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1232] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1233] R24 is hydrogen, [1234] Y is
--(CH.sub.2).sub.n--, [1235] n is 0 or 1, [1236] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1237] R4 --C(O)--O-1-4C-alkyl, which is
optionally substituted by R43, [1238] R43 is hydroxy, [1239] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1240] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1241] R71 is
1-4C-alkoxy or hydroxy, [1242] R72 is 1-4C-alkoxy or hydroxy,
[1243] R73 is 1-4C-alkoxy or hydroxy, [1244] R8 is hydrogen, [1245]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1246] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1247] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1248] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1249] R11 is 1-4C-alkoxy or hydroxy, [1250]
R21 is hydrogen, [1251] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1252] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1253] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1254] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1255] R24 is hydrogen, [1256] Y is
--(CH.sub.2).sub.n--, [1257] n is 0 or 1, [1258] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1259] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1260] R41 is
1-4C-alkoxy or hydroxy, [1261] R42 is 1-4C-alkoxy or hydroxy,
[1262] R43 is 1-4C-alkoxy or hydroxy, [1263] R6 is --NH--C(O)--R7,
[1264] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1265] R71 is
1-4C-alkoxy or hydroxy, [1266] R72 is 1-4C-alkoxy or hydroxy,
[1267] R73 is 1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of
the compound or the salt thereof and a stereoisomer of the
compound, the salt, the N-oxide of the compound or the N-oxide of
the salt thereof.
[1268] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1269] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1270] R11 is 1-4C-alkoxy or hydroxy, [1271]
R21 is hydrogen, [1272] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1273] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1274] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1275] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1276] R24 is hydrogen, [1277] Y is
--(CH.sub.2).sub.n--, [1278] n is 0 or 1, [1279] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1280] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1281] R41 is
1-4C-alkoxy or hydroxy, [1282] R42 is 1-4C-alkoxy or hydroxy,
[1283] R43 is 1-4C-alkoxy or hydroxy, [1284] R6 is --C(O)--NR8R9,
[1285] R8 is hydrogen, [1286] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [1287] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1288] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1289] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1290] R11 is 1-4C-alkoxy or hydroxy, [1291]
R21 is hydrogen, [1292] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1293] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1294] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1295] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1296] R24 is hydrogen, [1297] Y is
--(CH.sub.2).sub.n--, [1298] n is 0 or 1, [1299] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1300] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1301] R41 is
1-4C-alkoxy or hydroxy, [1302] R42 is 1-4C-alkoxy or hydroxy,
[1303] R43 is 1-4C-alkoxy or hydroxy, [1304] R6 is --NH--C(O)--R7,
[1305] R7 is 1-2C-alkyl, which is optionally substituted by R71,
[1306] R71 is 1-2C-alkoxy, [1307] R8 is hydrogen, [1308] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1309] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1310] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1311] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1312] R11 is 1-4C-alkoxy or hydroxy, [1313]
R21 is hydrogen, [1314] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1315] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1316] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1317] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1318] R24 is hydrogen, [1319] Y is
--(CH.sub.2).sub.n--, [1320] n is 0 or 1, [1321] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1322] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1323] R41 is
1-4C-alkoxy or hydroxy, [1324] R42 is 1-4C-alkoxy or hydroxy,
[1325] R43 is 1-4C-alkoxy or hydroxy, [1326] R6 is --NH--C(O)--R7,
[1327] R7 is 1-2C-alkyl, which is optionally substituted by R71,
[1328] R71 is hydroxy, [1329] R8 is hydrogen, [1330] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1331] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1332] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1333] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1334] R11 is 1-4C-alkoxy or hydroxy, [1335]
R21 is hydrogen, [1336] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1337] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1338] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1339] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1340] R24 is hydrogen, [1341] Y is
--(CH.sub.2).sub.n--, [1342] n is 0 or 1, [1343] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1344] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1345] R41 is
1-4C-alkoxy or hydroxy, [1346] R42 is 1-4C-alkoxy or hydroxy,
[1347] R43 is 1-4C-alkoxy or hydroxy, [1348] R6 is --NH--C(O)--R7,
[1349] R7 is cyclopropyl, which is optionally substituted by R72,
[1350] R72 is 1-2C-alkoxy, [1351] R8 is hydrogen, [1352] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1353] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1354] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1355] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1356] R11 is 1-4C-alkoxy or hydroxy, [1357]
R21 is hydrogen, [1358] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1359] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1360] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1361] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1362] R24 is hydrogen, [1363] Y is
--(CH.sub.2).sub.n--, [1364] n is 0 or 1, [1365] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1366] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1367] R41 is
1-4C-alkoxy or hydroxy, [1368] R42 is 1-4C-alkoxy or hydroxy,
[1369] R43 is 1-4C-alkoxy or hydroxy, [1370] R6 is --NH--C(O)--R7,
[1371] R7 is cyclopropyl, which is optionally substituted by R72,
[1372] R72 is hydroxy, [1373] R8 is hydrogen, [1374] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1375] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1376] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1377] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1378] R11 is 1-4C-alkoxy or hydroxy, [1379]
R21 is hydrogen, [1380] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1381] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1382] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1383] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1384] R24 is hydrogen, [1385] Y is
--(CH.sub.2).sub.n--, [1386] n is 0 or 1, [1387] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1388] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1389] R41 is
1-4C-alkoxy or hydroxy, [1390] R42 is 1-4C-alkoxy or hydroxy,
[1391] R43 is 1-4C-alkoxy or hydroxy, [1392] R6 is --NH--C(O)--R7,
[1393] R7 is 1-2C-alkoxy, [1394] R8 is hydrogen, [1395] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1396] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1397] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1398] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1399] R11 is 1-4C-alkoxy or hydroxy, [1400]
R21 is hydrogen, [1401] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1402] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1403] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1404] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1405] R24 is hydrogen, [1406] Y is
--(CH.sub.2).sub.n--, [1407] n is 0 or 1, [1408] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1409] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-2C-alkyl, wherein the
1-2C-alkyl group is optionally substituted by R43, [1410] R41 is
1-4C-alkoxy or hydroxy, [1411] R42 is 1-4C-alkoxy or hydroxy,
[1412] R43 is 1-4C-alkoxy or hydroxy, [1413] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [1414] R7 is 1-4C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-2C-alkoxy, which is optionally substituted
by R73, [1415] R71 is 1-4C-alkoxy or hydroxy, [1416] R72 is
1-4C-alkoxy or hydroxy, [1417] R73 is 1-4C-alkoxy or hydroxy,
[1418] R8 is hydrogen, [1419] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [1420] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1421] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1422] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1423] R11 is 1-4C-alkoxy or hydroxy, [1424]
R21 is hydrogen, [1425] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1426] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1427] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1428] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1429] R24 is hydrogen, [1430] Y is
--(CH.sub.2).sub.n--, [1431] n is 0 or 1, [1432] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1433] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41, or
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by [1434] R42, [1435] R41 is 1-4C-alkoxy or
hydroxy, [1436] R42 is 1-4C-alkoxy or hydroxy, [1437] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1438] R7 is 1-4C-alkyl,
which is optionally substituted by R71, or 3-6C-cycloalkyl, which
is optionally substituted by R72, [1439] R71 is 1-4C-alkoxy or
hydroxy, [1440] R72 is 1-4C-alkoxy or hydroxy, [1441] R8 is
hydrogen, [1442] R9 is 1-4C-alkyl, which is optionally substituted
by R91, or 3-6C-cycloalkyl, [1443] R91 is 1-4C-alkoxy or hydroxy,
salts thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1444] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1445] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1446] R11 is 1-4C-alkoxy or hydroxy, [1447]
R21 is hydrogen, [1448] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1449] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1450] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1451] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1452] R24 is hydrogen, [1453] Y is
--(CH.sub.2).sub.n--, [1454] n is 0 or 1, [1455] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1456] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1457] R41 is
1-4C-alkoxy or hydroxy, [1458] R42 is 1-4C-alkoxy or hydroxy,
[1459] R43 is 1-4C-alkoxy or hydroxy, [1460] R6 is --NH--C(O)--R7
or --C(O)--NR8R9, [1461] R7 is hydrogen, 1-4C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [1462] R71 is 1-4C-alkoxy or hydroxy, [1463] R72 is
1-4C-alkoxy or hydroxy, [1464] R73 is 1-4C-alkoxy or hydroxy,
[1465] R8 is hydrogen, [1466] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [1467] R91 is 1-4C-alkoxy
or hydroxy, salts thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1468] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1469] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1470] R11 is 1-4C-alkoxy or hydroxy, [1471]
R21 is hydrogen, [1472] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1473] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1474] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1475] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1476] R24 is hydrogen, [1477] Y is
--(CH.sub.2).sub.n--, [1478] n is 0 or 1, [1479] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1480] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41, or
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by [1481] R42, [1482] R41 is 1-4C-alkoxy or
hydroxy, [1483] R42 is 1-4C-alkoxy or hydroxy, [1484] R6 is
--NH--C(O)--R7 or --C(O)--NR8R9, [1485] R7 is 1-4C-alkyl, which is
optionally substituted by R71, or 3-6C-cycloalkyl, which is
optionally substituted by R72, [1486] R71 is 1-4C-alkoxy or
hydroxy, [1487] R72 is 1-4C-alkoxy or hydroxy, [1488] R8 is
hydrogen, [1489] R9 is 1-4C-alkyl, which is optionally substituted
by R91, or 3-6C-cycloalkyl, [1490] R91 is 1-4C-alkoxy or hydroxy,
salts thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1491] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1492] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1493] R11 is 1-4C-alkoxy or hydroxy, [1494]
R21 is hydrogen, [1495] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1496] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1497] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1498] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1499] R24 is hydrogen, [1500] Y is
--(CH.sub.2).sub.n--, [1501] n is 0 or 1, [1502] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1503] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1504] R41 is
1-4C-alkoxy or hydroxy, [1505] R42 is 1-4C-alkoxy or hydroxy,
[1506] R43 is 1-4C-alkoxy or hydroxy, [1507] R6 is --C(O)--NR8R9,
[1508] R8 is hydrogen, [1509] R9 is 1-2C-alkyl, which is optionally
substituted by R91, [1510] R91 is 1-2C-alkoxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[1511] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1512] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1513] R11 is 1-4C-alkoxy or hydroxy, [1514]
R21 is hydrogen, [1515] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1516] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1517] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1518] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1519] R24 is hydrogen, [1520] Y is
--(CH.sub.2).sub.n--, [1521] n is 0 or 1, [1522] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1523] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1524] R41 is
1-4C-alkoxy or hydroxy, [1525] R42 is 1-4C-alkoxy or hydroxy,
[1526] R43 is 1-4C-alkoxy or hydroxy, [1527] R6 is --C(O)--NR8R9,
[1528] R8 is hydrogen, [1529] R9 is 1-2C-alkyl, which is optionally
substituted by R91, [1530] R91 is hydroxy, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[1531] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1532] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1533] R11 is 1-4C-alkoxy or hydroxy, [1534]
R21 is hydrogen, [1535] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1536] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1537] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1538] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1539] R24 is hydrogen, [1540] Y is
--(CH.sub.2).sub.n--, [1541] n is 0 or 1, [1542] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1543] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1544] R41 is
1-4C-alkoxy or hydroxy, [1545] R42 is 1-4C-alkoxy or hydroxy,
[1546] R43 is 1-4C-alkoxy or hydroxy, [1547] R6 is --C(O)--NR8R9,
[1548] R8 is hydrogen, [1549] R9 is cyclopropyl, a salt thereof, an
N-oxide of the compound or the salt thereof and a stereoisomer of
the compound, the salt, the N-oxide of the compound or the N-oxide
of the salt thereof.
[1550] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1551] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1552] R11 is 1-4C-alkoxy or hydroxy, [1553]
R21 is hydrogen, [1554] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1555] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1556] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1557] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1558] R24 is hydrogen, [1559] Y is
--(CH.sub.2).sub.n--, [1560] n is 0 or 1, [1561] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, [1562] wherein R4, if present, is
bonded to said nitrogen atom, [1563] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [1564] R41 is 1-4C-alkoxy or hydroxy, [1565]
R42 is 1-4C-alkoxy or hydroxy, [1566] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1567] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1568] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1569] R11 is 1-4C-alkoxy or hydroxy, [1570]
R21 is hydrogen, [1571] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1572] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1573] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1574] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1575] R24 is hydrogen, [1576] Y is
--(CH.sub.2).sub.n--, [1577] n is 0 or 1, [1578] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
substituted by R4 at said nitrogen atom, [1579] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [1580] R41 is 1-4C-alkoxy or hydroxy, [1581]
R42 is 1-4C-alkoxy or hydroxy, [1582] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1583] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1584] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [1585] R11 is 1-4C-alkoxy, [1586] R21 is
hydrogen, [1587] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [1588] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [1589] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [1590] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1591] R24 is hydrogen, [1592] Y is
--(CH.sub.2).sub.n--, [1593] n is 0 or 1, [1594] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
substituted by R4 at said nitrogen atom, [1595] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [1596] R41 is 1-4C-alkoxy or hydroxy, [1597]
R42 is 1-4C-alkoxy or hydroxy, [1598] R43 is 1-4C-alkoxy or
hydroxy, salts thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1599] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1600] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1601] R21 is hydrogen, [1602] R22 is
hydrogen, [1603] R23 is hydrogen, [1604] R24 is hydrogen, [1605] Y
is --(CH.sub.2).sub.n--, [1606] n is 0, [1607] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1608] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl or --C(O)--O-1-4C-alkyl, [1609] R41 is hydroxy,
[1610] R6 is --NH--C(O)--R7 or NH.sub.2, [1611] R7 is 1-2C-alkyl,
which is optionally substituted by R71, cyclopropyl, which is
optionally substituted by R72, or 1-2C-alkoxy, which is optionally
substituted by R73, [1612] R71 is 1-2C-alkoxy or hydroxy, [1613]
R72 is hydroxy, [1614] R73 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1615] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1616] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1617] R21 is hydrogen, [1618] R22 is
hydrogen, [1619] R23 is 1-4C-alkoxy, [1620] R24 is hydrogen, [1621]
Y is --(CH.sub.2).sub.n--, [1622] n is 0, [1623] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1624] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein cyclopropyl group is optionally
substituted by R42, --C(O)--O-1-4C-alkyl, [1625] R41 is 1-2C-alkoxy
or hydroxy, [1626] R42 is hydroxy, [1627] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [1628] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [1629] R71 is 1-2C-alkoxy or
hydroxy, [1630] R72 is hydroxy, [1631] R8 is hydrogen, [1632] R9 is
1-2C-alkyl, which is optionally substituted by R91, or cyclopropyl,
[1633] R91 is 1-2C-alkoxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1634] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1635] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1636] R21 is hydrogen, [1637] R22 is
halogen, [1638] R23 is 1-4C-alkoxy, [1639] R24 is hydrogen, [1640]
Y is --(CH.sub.2).sub.n--, [1641] n is 0, [1642] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4, or
a cyclohexyl group substituted by R6, [1643] R4 is
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclopropyl, wherein the cyclopropyl
group is optionally substituted by R42, or --C(O)--O-1-4C-alkyl,
[1644] R41 is 1-2C-alkoxy or hydroxy, [1645] R42 is hydroxy, [1646]
R6 is --NH--C(O)--R7 or NH.sub.2, [1647] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [1648] R71 is 1-2C-alkoxy or
hydroxy, [1649] R72 is hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1650] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1651] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1652] R21 is hydrogen, [1653] R22 is
--C(O)-1-4C-alkyl, [1654] R23 is hydrogen, [1655] R24 is hydrogen,
[1656] Y is --(CH.sub.2).sub.n--, [1657] n is 0, [1658] R3 is a
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[1659] R4 is --C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is
optionally substituted by R41, [1660] R41 is 1-2C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1661] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1662] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1663] R21 is hydrogen, [1664] R22 is
halogen, [1665] R23 is hydrogen, [1666] R24 is hydrogen, [1667] Y
is --(CH.sub.2).sub.n--, [1668] n is 0, [1669] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1670] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41, or
--C(O)--O-1-4C-alkyl, [1671] R41 is 1-2C-alkoxy or hydroxy, [1672]
R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1673] R7 is
1-2C-alkyl, which is optionally substituted by R71, or 1-4C-alkoxy,
[1674] R71 is 1-2C-alkoxy or hydroxy, [1675] R8 is hydrogen, [1676]
R9 is 1-2C-alkyl, which is optionally substituted by R91, or
cyclopropyl, [1677] R91 is 1-2C-alkoxy, a salt thereof, an N-oxide
of the compound or the salt thereof and a stereoisomer of the
compound, the salt, the N-oxide of the compound or the N-oxide of
the salt thereof.
[1678] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1679] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1680] R21 is hydrogen, [1681] R22 is
1-4C-alkoxy, [1682] R23 is hydrogen, [1683] R24 is hydrogen, [1684]
Y is --(CH.sub.2).sub.n--, [1685] n is 0, [1686] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1687] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein the cyclopropyl group is optionally
substituted by R42, or --C(O)--O-1-4C-alkyl, [1688] R41 is
1-2C-alkoxy or hydroxy, [1689] R42 is hydroxy, [1690] R6 is
--NH--C(O)--R7 or NH.sub.2, [1691] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [1692] R71 is 1-2C-alkoxy or
hydroxy, [1693] R72 is hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1694] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1695] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1696] R21 is hydrogen, [1697] R22 is
1-4C-fluoroalkoxy, [1698] R23 is hydrogen, [1699] R24 is hydrogen,
[1700] Y is --(CH.sub.2).sub.n--, [1701] n is 0, [1702] R3 is a
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4, or
a cyclohexyl group substituted by R6, [1703] R4 is
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-- cyclopropyl, wherein the cyclopropyl
group is optionally substituted by R42, or --C(O)--O-1-4C-alkyl,
[1704] R41 is 1-2C-alkoxy or hydroxy, [1705] R42 is hydroxy, [1706]
R6 is --NH--C(O)--R7 or NH.sub.2, [1707] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [1708] R71 is 1-2C-alkoxy or
hydroxy, [1709] R72 is hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1710] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1711] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1712] R21 is hydrogen, [1713] R22 is
1-4C-alkoxy, [1714] R23 is halogen, [1715] R24 is hydrogen, [1716]
Y is --(CH.sub.2).sub.n--, [1717] n is 0, [1718] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[1719] R4 is --C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is
optionally substituted by R41, or --C(O)--O-1-4C-alkyl, [1720] R41
is 1-2C-alkoxy or hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1721] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1722] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1723] R21 is hydrogen, [1724] R22 is
1-4C-alkyl, [1725] R23 is hydrogen, [1726] R24 is hydrogen, [1727]
Y is --(CH.sub.2).sub.n--, [1728] n is 0, [1729] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1730] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein the cyclopropyl group is optionally
substituted by R42, or --C(O)--O-1-4C-alkyl, [1731] R41 is
1-2C-alkoxy or hydroxy, [1732] R42 is hydroxy, [1733] R6 is
--NH--C(O)--R7, or NH.sub.2, [1734] R7 is 1-2C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [1735] R71 is 1-2C-alkoxy or
hydroxy, [1736] R72 is hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1737] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1738] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1739] R21 and R22 combine to form a
group --O--CH.sub.2--O--, [1740] R23 is hydrogen, [1741] R24 is
hydrogen, [1742] Y is --(CH.sub.2).sub.n--, [1743] n is 0 or 1,
[1744] R3 is a 4- to 6-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1745] R4 is --C(O)--H,
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclohexyl, wherein the cyclohexyl group
is optionally substituted by R42, or --C(O)--O-1-4C-alkyl, [1746]
R41 is 1-2C-alkoxy or hydroxy, [1747] R42 is hydroxy, [1748] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1749] R7 is 1-2C-alkyl,
which is optionally substituted by R71, cyclopropyl, which is
optionally substituted by R72, or 1-4C-alkoxy, [1750] R71 is
1-2C-alkoxy or hydroxy, [1751] R72 is hydroxy, [1752] R8 is
hydrogen, [1753] R9 is 1-2C-alkyl, which is optionally substituted
by R91, or cyclopropyl, [1754] R91 is 1-2C-alkoxy or hydroxy, a
salt thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1755] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1756] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1757] R21 and R22 combine to form a
group --O--CH.sub.2--O--, [1758] R23 is hydrogen, [1759] R24 is
hydrogen, [1760] Y is --(CH.sub.2).sub.n--, [1761] n is 0, [1762]
R3 is a 4- to 6-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a cyclohexyl group
substituted by R6, [1763] R4 is --C(O)--H, --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein the cyclopropyl group is optionally
substituted by R42, or --C(O)---1-4C-alkyl, [1764] R41 is
1-2C-alkoxy or hydroxy, [1765] R42 is hydroxy, [1766] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [1767] R7 is 1-2C-alkyl,
which is optionally substituted by R71, cyclopropyl, which is
optionally substituted by R72, or 1-4C-alkoxy, [1768] R71 is
1-2C-alkoxy or hydroxy, [1769] R72 is hydroxy, [1770] R8 is
hydrogen, [1771] R9 is 1-2C-alkyl, which is optionally substituted
by R91, or cyclopropyl, [1772] R91 is 1-2C-alkoxy or hydroxy, a
salt thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1773] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1774] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1775] R21 and R22 combine to form a
group --O--CH.sub.2--O--, [1776] R23 is hydrogen, [1777] R24 is
hydrogen, [1778] Y is --(CH.sub.2).sub.n--, [1779] n is 1, [1780]
R3 is a 5- to 6-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, [1781] R4 is --C(O)--H,
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclopropyl, wherein the cyclopropyl
group is optionally substituted by R42, or --C(O)---1-4C-alkyl,
[1782] R41 is 1-2C-alkoxy or hydroxy, [1783] R42 is hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof. [1784] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1785] R21 is hydrogen, [1786] R22 is
halogen, [1787] R23 is 1-4C-alkoxy, [1788] R24 is hydrogen, [1789]
Y is --(CH.sub.2).sub.n--, [1790] n is 0 or 1, [1791] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being substituted by R4, [1792] R4 is
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, [1793] R41 is 1-4C-alkoxy or hydroxy, salts
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1794] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1795] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1796] R21 is hydrogen, [1797] R22 is
hydrogen, [1798] R23 is halogen, [1799] R24 is hydrogen, [1800] Y
is --(CH.sub.2).sub.n--, [1801] n is 0, [1802] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [1803] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41, or
--C(O)--O-1-4C-alkyl, [1804] R41 is 1-2C-alkoxy or hydroxy, [1805]
R6 is --NH--C(O)--R7 or NH.sub.2, [1806] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [1807] R71 is 1-2C-alkoxy or
hydroxy, [1808] R72 is hydroxy, a salt thereof, an N-oxide of the
compound or the salt thereof and a stereoisomer of the compound,
the salt, the N-oxide of the compound or the N-oxide of the salt
thereof.
[1809] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1810] R1 1-4C-alkyl which is
optionally substituted by R11, [1811] R11 is 1-4C-alkoxy or
hydroxy, [1812] R21 is hydrogen, [1813] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [1814] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [1815] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [1816] or R22 and R23
combine to form a group --O--CH.sub.2--O-- [1817] R24 is hydrogen,
[1818] Y is --(CH.sub.2).sub.n--, [1819] n is 0 or 1, [1820] R3 is
a 6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[1821] R4 is --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, [1822] R41 is 1-2C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1823] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1824] R1 1-4C-alkyl which is
optionally substituted by R11, [1825] R11 is 1-4C-alkoxy or
hydroxy, [1826] R21 is hydrogen, [1827] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [1828] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [1829] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [1830] or R22 and R23
combine to form a group --O--CH.sub.2--O-- [1831] R24 is hydrogen,
[1832] Y is --(CH.sub.2).sub.n--, [1833] n is 0, [1834] R3 is a
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[1835] R4 is --C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is
optionally substituted by R41, [1836] R41 is 1-2C-alkoxy or
hydroxy, a salt thereof, an N-oxide of the compound or the salt
thereof and a stereoisomer of the compound, the salt, the N-oxide
of the compound or the N-oxide of the salt thereof.
[1837] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1838] R1 1-4C-alkyl which is
optionally substituted by R11, [1839] R11 is 1-4C-alkoxy or
hydroxy, [1840] R21 is hydrogen, [1841] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [1842] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [1843] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [1844] or R22 and R23
combine to form a group --O--CH.sub.2--O-- [1845] R24 is hydrogen,
[1846] Y is --(CH.sub.2).sub.n--, [1847] n is 0 or 1, [1848] R3 is
a 4- to 7-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1849] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1850] R41 is
1-4C-alkoxy or hydroxy, [1851] R42 is 1-4C-alkoxy or hydroxy,
[1852] R43 is 1-4C-alkoxy or hydroxy, [1853] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [1854] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [1855] R71 is 1-4C-alkoxy or hydroxy, [1856]
R72 is 1-4C-alkoxy or hydroxy, [1857] R73 is 1-4C-alkoxy or
hydroxy, [1858] R8 is hydrogen, [1859] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [1860] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[1861] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1862] R1 3-4C-alkyl, [1863] R21
is hydrogen, [1864] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1865] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1866] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1867] or R22 and R23 combine to form a group
--O--CH.sub.2--O-- [1868] R24 is hydrogen, [1869] Y is
--(CH.sub.2).sub.n--, [1870] n is 0 or 1, [1871] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1872] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1873] R41 is
1-4C-alkoxy or hydroxy, [1874] R42 is 1-4C-alkoxy or hydroxy,
[1875] R43 is 1-4C-alkoxy or hydroxy, [1876] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [1877] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [1878] R71 is 1-4C-alkoxy or hydroxy, [1879]
R72 is 1-4C-alkoxy or hydroxy, [1880] R73 is 1-4C-alkoxy or
hydroxy, [1881] R8 is hydrogen, [1882] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [1883] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[1884] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1885] R1 3-4C-alkyl, [1886] R21
and R22 combine to form a group --O--CH.sub.2--O--, [1887] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [1888] R24 is hydrogen, [1889] Y is
--(CH.sub.2).sub.n--, [1890] n is 0 or 1, [1891] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1892] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1893] R41 is
1-4C-alkoxy or hydroxy, [1894] R42 is 1-4C-alkoxy or hydroxy,
[1895] R43 is 1-4C-alkoxy or hydroxy, [1896] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [1897] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [1898] R71 is 1-4C-alkoxy or hydroxy, [1899]
R72 is 1-4C-alkoxy or hydroxy, [1900] R73 is 1-4C-alkoxy or
hydroxy, [1901] R8 is hydrogen, [1902] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [1903] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, an N-oxide of the compound
or the salt thereof and a stereoisomer of the compound, the salt,
the N-oxide of the compound or the N-oxide of the salt thereof.
[1904] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1905] R1 3-4C-alkyl, [1906] R21
and R22 combine to form a group --O--CH.sub.2--O--, [1907] R23 is
hydrogen, [1908] R24 is hydrogen, [1909] Y is --(CH.sub.2).sub.n--,
[1910] n is 0 or 1, [1911] R3 is a 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom, said heterocyclic ring being optionally substituted by
R4, or a 3-6C-cycloalkyl group substituted by R6, [1912] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [1913] R41 is 1-4C-alkoxy or hydroxy, [1914]
R42 is 1-4C-alkoxy or hydroxy, [1915] R43 is 1-4C-alkoxy or
hydroxy, [1916] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[1917] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1918] R71 is
1-4C-alkoxy or hydroxy, [1919] R72 is 1-4C-alkoxy or hydroxy,
[1920] R73 is 1-4C-alkoxy or hydroxy, [1921] R8 is hydrogen, [1922]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [1923] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, an N-oxide of the compound or the salt thereof and a
stereoisomer of the compound, the salt, the N-oxide of the compound
or the N-oxide of the salt thereof.
[1924] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1925] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [1926] R11 is 1-4C-alkoxy or hydroxy, [1927]
R21 is hydrogen, [1928] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1929] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1930] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1931] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [1932] R24 is hydrogen, [1933] Y is
--(CH.sub.2).sub.n--, [1934] n is 0 or 1, [1935] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [1936] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [1937] R41 is
1-4C-alkoxy or hydroxy, [1938] R42 is 1-4C-alkoxy or hydroxy,
[1939] R43 is 1-4C-alkoxy or hydroxy, [1940] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [1941] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [1942] R71 is 1-4C-alkoxy or hydroxy, [1943]
R72 is 1-4C-alkoxy or hydroxy, [1944] R73 is 1-4C-alkoxy or
hydroxy, [1945] R8 is hydrogen, [1946] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [1947] R91 is 1-4C-alkoxy or
hydroxy, [1948] R92 is 1-4C-alkoxy or hydroxy, salts thereof, and
stereoisomers of the compounds and the salts thereof.
[1949] In a preferred embodiment, the invention relates to
compounds of formula (I), wherein [1950] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [1951] R11 is 1-4C-alkoxy or hydroxy, [1952]
R21 is hydrogen, [1953] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[1954] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[1955] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [1956] R24 is hydrogen, [1957] Y is
--(CH.sub.2).sub.n--, [1958] n is 0 or 1, [1959] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, [1960] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [1961] R41 is 1-4C-alkoxy or hydroxy, [1962]
R42 is 1-4C-alkoxy or hydroxy, [1963] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[1964] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1965] R1 is
--CH.sub.2-3-4C-cycloalkyl, [1966] R21 is hydrogen, [1967] R22 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy,
1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [1968] or R21 and R22
combine to form a group --O--CH.sub.2--O--, [1969] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[1970] or R22 and R23 combine to form a group --O--CH.sub.2--O--,
[1971] R24 is hydrogen, [1972] Y is --(CH.sub.2).sub.n--, [1973] n
is 0 or 1, [1974] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [1975] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [1976] R41 is 1-4C-alkoxy or hydroxy, [1977]
R42 is 1-4C-alkoxy or hydroxy, [1978] R43 is 1-4C-alkoxy or
hydroxy, [1979] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[1980] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [1981] R71 is
1-4C-alkoxy or hydroxy, [1982] R72 is 1-4C-alkoxy or hydroxy,
[1983] R73 is 1-4C-alkoxy or hydroxy, [1984] R8 is hydrogen, [1985]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, which is optionally substituted by R92, [1986] R91
is 1-4C-alkoxy or hydroxy, [1987] R92 is 1-4C-alkoxy or hydroxy, a
salt thereof, or a stereoisomer of the compound or the salt
thereof.
[1988] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [1989] R1 is 1-4C-alkyl which is
optionally substituted by R11, [1990] R11 is 1-4C-alkoxy or
hydroxy, [1991] R21 is hydrogen, [1992] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [1993] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [1994] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [1995] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [1996] R24 is hydrogen,
[1997] Y is --(CH.sub.2).sub.n--, [1998] n is 0 or 1, [1999] R3 is
a 4- to 7-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2000] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2001] R41 is
1-4C-alkoxy or hydroxy, [2002] R42 is 1-4C-alkoxy or hydroxy,
[2003] R43 is 1-4C-alkoxy or hydroxy, [2004] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2005] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2006] R71 is 1-4C-alkoxy or hydroxy, [2007]
R72 is 1-4C-alkoxy or hydroxy, [2008] R73 is 1-4C-alkoxy or
hydroxy, [2009] R8 is hydrogen, [2010] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [2011] R91 is 1-4C-alkoxy or
hydroxy, [2012] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2013] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2014] R1 is 3-4C-alkyl which is
optionally substituted by R11, [2015] R11 is methoxy, [2016] R21 is
hydrogen, [2017] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [2018] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [2019] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2020] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2021] R24 is hydrogen, [2022] Y is
--(CH.sub.2).sub.n--, [2023] n is 0 or 1, [2024] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2025] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2026] R41 is
1-4C-alkoxy or hydroxy, [2027] R42 is 1-4C-alkoxy or hydroxy,
[2028] R43 is 1-4C-alkoxy or hydroxy, [2029] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2030] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2031] R71 is 1-4C-alkoxy or hydroxy, [2032]
R72 is 1-4C-alkoxy or hydroxy, [2033] R73 is 1-4C-alkoxy or
hydroxy, [2034] R8 is hydrogen, [2035] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2036] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2037] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2038] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2039] R11 is 1-4C-alkoxy or hydroxy, [2040]
R21 is hydrogen, [2041] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2042] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2043] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2044] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2045] R24 is hydrogen, [2046] Y is
--(CH.sub.2).sub.n--, [2047] n is 0 or 1, [2048] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[2049] R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl
group is optionally substituted by R41, --C(O)-3-6C-cycloalkyl,
wherein the 3-6C-cycloalkyl group is optionally substituted by R42,
or --C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2050] R41 is 1-4C-alkoxy or hydroxy, [2051]
R42 is 1-4C-alkoxy or hydroxy, [2052] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[2053] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2054] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [2055] R11 is 1-4C-alkoxy or hydroxy, [2056]
R21 is hydrogen, [2057] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2058] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2059] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2060] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2061] R24 is hydrogen, [2062] Y is
--(CH.sub.2).sub.n--, [2063] n is 0 or 1, [2064] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being substituted by R4, [2065] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2066] R41 is 1-4C-alkoxy or hydroxy, [2067]
R42 is 1-4C-alkoxy or hydroxy, [2068] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[2069] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2070] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [2071] R11 is 1-4C-alkoxy or hydroxy, [2072]
R21 is hydrogen, [2073] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2074] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2075] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2076] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2077] R24 is hydrogen, [2078] Y is
--(CH.sub.2).sub.n--, [2079] n is 0 or 1, [2080] R3 is a
3-6C-cycloalkyl group substituted by R6, [2081] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [2082] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2083] R71 is
1-4C-alkoxy or hydroxy, [2084] R72 is 1-4C-alkoxy or hydroxy,
[2085] R73 is 1-4C-alkoxy or hydroxy, [2086] R8 is hydrogen, [2087]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, which is optionally substituted by R92, [2088] R91
is 1-4C-alkoxy or hydroxy, [2089] R92 is 1-4C-alkoxy or hydroxy, a
salt thereof, or a stereoisomer of the compound or the salt
thereof.
[2090] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2091] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [2092] R11 is 1-4C-alkoxy or hydroxy, [2093]
R21 is hydrogen, [2094] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2095] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2096] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2097] R24 is hydrogen, [2098] Y is
--(CH.sub.2).sub.n--, [2099] n is 0 or 1, [2100] R3 is a cyclohexyl
group substituted by R6, [2101] R6 is --NH--C(O)--R7, --C(O)--NR8R9
or NH.sub.2, [2102] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [2103] R71 is 1-4C-alkoxy or hydroxy, [2104] R72 is
1-4C-alkoxy or hydroxy, [2105] R73 is 1-4C-alkoxy or hydroxy,
[2106] R8 is hydrogen, [2107] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, which is optionally
substituted by R92, [2108] R91 is 1-4C-alkoxy or hydroxy, [2109]
R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of
the compound or the salt thereof.
[2110] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2111] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2112] R11 is 1-4C-alkoxy or hydroxy, [2113]
R21 is hydrogen, [2114] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2115] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2116] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2117] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2118] R24 is hydrogen, [2119] Y is
--(CH.sub.2).sub.n--, [2120] n is 0 or 1, [2121] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and one oxygen atom, said heterocyclic ring being optionally
substituted by R4, [2122] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2123] R41 is
1-4C-alkoxy or hydroxy, [2124] R42 is 1-4C-alkoxy or hydroxy,
[2125] R43 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2126] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2127] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [2128] R11 is 1-4C-alkoxy, [2129] R21 is
hydrogen, [2130] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [2131] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [2132] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2133] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2134] R24 is hydrogen, [2135] Y is
--(CH.sub.2).sub.n--, [2136] n is 0 or 1, [2137] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and one oxygen atom, said heterocyclic ring being substituted by
R4, [2138] R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2139] R41 is
1-4C-alkoxy or hydroxy, [2140] R42 is 1-4C-alkoxy or hydroxy,
[2141] R43 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2142] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2143] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2144] R11 is 1-4C-alkoxy or hydroxy, [2145]
R21 is hydrogen, [2146] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2147] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2148] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2149] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2150] R24 is hydrogen, [2151] Y is
--(CH.sub.2).sub.n--, [2152] n is 0 or 1, [2153] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being substituted by R4, [2154] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2155] R41 is 1-4C-alkoxy or hydroxy, [2156]
R42 is 1-4C-alkoxy or hydroxy, [2157] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[2158] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2159] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2160] R11 is 1-4C-alkoxy or hydroxy, [2161]
R21 is hydrogen, [2162] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2163] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2164] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2165] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2166] R24 is hydrogen, [2167] Y is
--(CH.sub.2).sub.n--, [2168] n is 0 or 1, [2169] R3 is a 5-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being substituted by R4, [2170] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2171] R41 is 1-4C-alkoxy or hydroxy, [2172]
R42 is 1-4C-alkoxy or hydroxy, [2173] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[2174] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2175] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2176] R11 is 1-4C-alkoxy or hydroxy, [2177]
R21 is hydrogen, [2178] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2179] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2180] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2181] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2182] R24 is hydrogen, [2183] Y is
--(CH.sub.2).sub.n--, [2184] n is 0 or 1, [2185] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being substituted by R4, [2186] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2187] R41 is 1-4C-alkoxy or hydroxy, [2188]
R42 is 1-4C-alkoxy or hydroxy, [2189] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[2190] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2191] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2192] R11 is 1-4C-alkoxy, [2193] R21 is
hydrogen, [2194] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [2195] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [2196] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2197] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2198] R24 is hydrogen, [2199] Y is
--(CH.sub.2).sub.n--, [2200] n is 0 or 1, [2201] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom and one
oxygen atom, said heterocyclic ring being substituted by R4, [2202]
R4 is --C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2203] R41 is 1-4C-alkoxy or hydroxy, [2204]
R42 is 1-4C-alkoxy or hydroxy, [2205] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[2206] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2207] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2208] R11 is 1-4C-alkoxy or hydroxy, [2209]
R21 is hydrogen, [2210] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or --C(O)-1-4C-alkyl, [2211] or R21 and R22
combine to form a group --O--CH.sub.2--O--, [2212] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy or hydroxy, [2213] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [2214] R24 is hydrogen,
[2215] Y is --(CH.sub.2).sub.n--, [2216] n is 0 or 1, [2217] R3 is
a 3-6C-cycloalkyl group substituted by R6, [2218] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [2219] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2220] R71 is
1-4C-alkoxy or hydroxy, [2221] R72 is 1-4C-alkoxy or hydroxy,
[2222] R73 is 1-4C-alkoxy or hydroxy, [2223] R8 is hydrogen, [2224]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, which is optionally substituted by R92, [2225] R91
is 1-4C-alkoxy or hydroxy, [2226] R92 is 1-4C-alkoxy or hydroxy, a
salt thereof, or a stereoisomer of the compound or the salt
thereof.
[2227] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2228] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2229] R11 is 1-4C-alkoxy or hydroxy, [2230]
R21 is hydrogen, [2231] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or --C(O)-1-4C-alkyl, [2232] or R21 and R22
combine to form a group --O--CH.sub.2--O--, [2233] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy or hydroxy, [2234] or R22 and R23
combine to form a group --O--CH.sub.2--O--, [2235] R24 is hydrogen,
[2236] Y is --(CH.sub.2).sub.n--, [2237] n is 0 or 1, [2238] R3 is
a cyclohexyl group substituted by R6, [2239] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2240] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2241] R71 is 1-4C-alkoxy or hydroxy, [2242]
R72 is 1-4C-alkoxy or hydroxy, [2243] R73 is 1-4C-alkoxy or
hydroxy, [2244] R8 is hydrogen, [2245] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2246] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2247] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2248] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2249] R11 is 1-4C-alkoxy or hydroxy, [2250]
R21 is hydrogen, [2251] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2252] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2253] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2254] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2255] R24 is hydrogen, [2256] Y is
--(CH.sub.2).sub.n--, [2257] n is 0, [2258] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2259] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2260] R41 is
1-4C-alkoxy or hydroxy, [2261] R42 is 1-4C-alkoxy or hydroxy,
[2262] R43 is 1-4C-alkoxy or hydroxy, [2263] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2264] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2265] R71 is 1-4C-alkoxy or hydroxy, [2266]
R72 is 1-4C-alkoxy or hydroxy, [2267] R73 is 1-4C-alkoxy or
hydroxy, [2268] R8 is hydrogen, [2269] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [2270] R91 is 1-4C-alkoxy or
hydroxy, [2271] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2272] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2273] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2274] R11 is 1-4C-alkoxy or hydroxy, [2275]
R21 is hydrogen, [2276] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2277] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2278] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2279] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2280] R24 is hydrogen, [2281] Y is
--(CH.sub.2).sub.n--, [2282] n is 1, [2283] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2284] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2285] R41 is
1-4C-alkoxy or hydroxy, [2286] R42 is 1-4C-alkoxy or hydroxy,
[2287] R43 is 1-4C-alkoxy or hydroxy, [2288] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2289] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2290] R71 is 1-4C-alkoxy or hydroxy, [2291]
R72 is 1-4C-alkoxy or hydroxy, [2292] R73 is 1-4C-alkoxy or
hydroxy, [2293] R8 is hydrogen, [2294] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [2295] R91 is 1-4C-alkoxy or
hydroxy, [2296] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2297] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2298] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2299] R11 is 1-4C-alkoxy or hydroxy, [2300]
R21 is hydrogen, [2301] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2302] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2303] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2304] R24 is hydrogen, [2305] Y is
--(CH.sub.2).sub.n--, [2306] n is 0 or 1, [2307] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2308] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2309] R41 is
1-4C-alkoxy or hydroxy, [2310] R42 is 1-4C-alkoxy or hydroxy,
[2311] R43 is 1-4C-alkoxy or hydroxy, [2312] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2313] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2314] R71 is 1-4C-alkoxy or hydroxy, [2315]
R72 is 1-4C-alkoxy or hydroxy, [2316] R73 is 1-4C-alkoxy or
hydroxy, [2317] R8 is hydrogen, [2318] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [2319] R91 is 1-4C-alkoxy or
hydroxy, [2320] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2321] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2322] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2323] R11 is 1-4C-alkoxy or hydroxy, [2324]
R21 and R22 combine to form a group --O--CH.sub.2--O--, [2325] R23
is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2326] R24 is hydrogen, [2327] Y is
--(CH.sub.2).sub.n--, [2328] n is 0 or 1, [2329] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2330] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2331] R41 is
1-4C-alkoxy or hydroxy, [2332] R42 is 1-4C-alkoxy or hydroxy,
[2333] R43 is 1-4C-alkoxy or hydroxy, [2334] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2335] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2336] R71 is 1-4C-alkoxy or hydroxy, [2337]
R72 is 1-4C-alkoxy or hydroxy, [2338] R73 is 1-4C-alkoxy or
hydroxy, [2339] R8 is hydrogen, [2340] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [2341] R91 is 1-4C-alkoxy or
hydroxy, [2342] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2343] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2344] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2345] R11 is 1-4C-alkoxy or hydroxy, [2346]
R21, R22, R23 and R24 are each hydrogen, [2347] Y is
--(CH.sub.2).sub.n--, [2348] n is 0 or 1, [2349] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2350] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2351] R41 is
1-4C-alkoxy or hydroxy, [2352] R42 is 1-4C-alkoxy or hydroxy,
[2353] R43 is 1-4C-alkoxy or hydroxy, [2354] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2355] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2356] R71 is 1-4C-alkoxy or hydroxy, [2357]
R72 is 1-4C-alkoxy or hydroxy, [2358] R73 is 1-4C-alkoxy or
hydroxy, [2359] R8 is hydrogen, [2360] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2361] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2362] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2363] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2364] R11 is 1-4C-alkoxy or hydroxy, [2365]
R21 is hydrogen, [2366] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2367] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2368] R23 is 1-4C-alkoxy, [2369] R24 is hydrogen, [2370] Y is
--(CH.sub.2).sub.n--, [2371] n is 0 or 1, [2372] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2373] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2374] R41 is
1-4C-alkoxy or hydroxy, [2375] R42 is 1-4C-alkoxy or hydroxy,
[2376] R43 is 1-4C-alkoxy or hydroxy, [2377] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2378] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2379] R71 is 1-4C-alkoxy or hydroxy, [2380]
R72 is 1-4C-alkoxy or hydroxy, [2381] R73 is 1-4C-alkoxy or
hydroxy, [2382] R8 is hydrogen, [2383] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2384] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2385] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2386] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2387] R11 is 1-4C-alkoxy or hydroxy, [2388]
R21 is hydrogen, [2389] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2390] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2391] R23 is hydroxy, [2392] R24 is hydrogen, [2393] Y is
--(CH.sub.2).sub.n--, [2394] n is 0 or 1, [2395] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2396] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2397] R41 is
1-4C-alkoxy or hydroxy, [2398] R42 is 1-4C-alkoxy or hydroxy,
[2399] R43 is 1-4C-alkoxy or hydroxy, [2400] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2401] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2402] R71 is 1-4C-alkoxy or hydroxy, [2403]
R72 is 1-4C-alkoxy or hydroxy, [2404] R73 is 1-4C-alkoxy or
hydroxy, [2405] R8 is hydrogen, [2406] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2407] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2408] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2409] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2410] R11 is 1-4C-alkoxy or hydroxy, [2411]
R21 is hydrogen, [2412] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2413] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2414] R23 is 1-4C-fluoroalkoxy, [2415] R24 is hydrogen, [2416] Y
is --(CH.sub.2).sub.n--, [2417] n is 0 or 1, [2418] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2419] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2420] R41 is
1-4C-alkoxy or hydroxy, [2421] R42 is 1-4C-alkoxy or hydroxy,
[2422] R43 is 1-4C-alkoxy or hydroxy, [2423] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2424] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2425] R71 is 1-4C-alkoxy or hydroxy, [2426]
R72 is 1-4C-alkoxy or hydroxy, [2427] R73 is 1-4C-alkoxy or
hydroxy, [2428] R8 is hydrogen, [2429] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2430] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2431] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2432] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2433] R11 is 1-4C-alkoxy or hydroxy, [2434]
R21 is hydrogen, [2435] R22 is halogen, [2436] R23 is 1-4C-alkoxy,
[2437] R24 is hydrogen, [2438] Y is --(CH.sub.2).sub.n--, [2439] n
is 0 or 1, [2440] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2441] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2442] R41 is 1-4C-alkoxy or hydroxy, [2443]
R42 is 1-4C-alkoxy or hydroxy, [2444] R43 is 1-4C-alkoxy or
hydroxy, [2445] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2446] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2447] R71 is
1-4C-alkoxy or hydroxy, [2448] R72 is 1-4C-alkoxy or hydroxy,
[2449] R73 is 1-4C-alkoxy or hydroxy, [2450] R8 is hydrogen, [2451]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2452] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2453] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2454] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2455] R11 is 1-4C-alkoxy or hydroxy, [2456]
R21 is hydrogen, [2457] R22 is --C(O)-1-4C-alkyl, [2458] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2459] R24 is hydrogen, [2460] Y is
--(CH.sub.2).sub.n--, [2461] n is 0 or 1, [2462] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2463] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2464] R41 is
1-4C-alkoxy or hydroxy, [2465] R42 is 1-4C-alkoxy or hydroxy,
[2466] R43 is 1-4C-alkoxy or hydroxy, [2467] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2468] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2469] R71 is 1-4C-alkoxy or hydroxy, [2470]
R72 is 1-4C-alkoxy or hydroxy, [2471] R73 is 1-4C-alkoxy or
hydroxy, [2472] R8 is hydrogen, [2473] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2474] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2475] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2476] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2477] R11 is 1-4C-alkoxy or hydroxy, [2478]
R21 is hydrogen, [2479] R22 is halogen, [2480] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2481] R24 is hydrogen, [2482] Y is --(CH.sub.2).sub.n--, [2483] n
is 0 or 1, [2484] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2485] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2486] R41 is 1-4C-alkoxy or hydroxy, [2487]
R42 is 1-4C-alkoxy or hydroxy, [2488] R43 is 1-4C-alkoxy or
hydroxy, [2489] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2490] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2491] R71 is
1-4C-alkoxy or hydroxy, [2492] R72 is 1-4C-alkoxy or hydroxy,
[2493] R73 is 1-4C-alkoxy or hydroxy, [2494] R8 is hydrogen, [2495]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2496] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2497] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2498] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2499] R11 is 1-4C-alkoxy or hydroxy, [2500]
R21 is hydrogen, [2501] R22 is 1-4C-alkoxy, [2502] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2503] R24 is hydrogen, [2504] Y is --(CH.sub.2).sub.n--, [2505] n
is 0 or 1, [2506] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2507] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2508] R41 is 1-4C-alkoxy or hydroxy, [2509]
R42 is 1-4C-alkoxy or hydroxy, [2510] R43 is 1-4C-alkoxy or
hydroxy, [2511] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2512] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2513] R71 is
1-4C-alkoxy or hydroxy, [2514] R72 is 1-4C-alkoxy or hydroxy,
[2515] R73 is 1-4C-alkoxy or hydroxy, [2516] R8 is hydrogen, [2517]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2518] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2519] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2520] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2521] R11 is 1-4C-alkoxy or hydroxy, [2522]
R21 is hydrogen, [2523] R22 is hydroxy, [2524] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2525] R24 is hydrogen, [2526] Y is --(CH.sub.2).sub.n--, [2527] n
is 0 or 1, [2528] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2529] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2530] R41 is 1-4C-alkoxy or hydroxy, [2531]
R42 is 1-4C-alkoxy or hydroxy, [2532] R43 is 1-4C-alkoxy or
hydroxy, [2533] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2534] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2535] R71 is
1-4C-alkoxy or hydroxy, [2536] R72 is 1-4C-alkoxy or hydroxy,
[2537] R73 is 1-4C-alkoxy or hydroxy, [2538] R8 is hydrogen, [2539]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2540] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2541] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2542] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2543] R11 is 1-4C-alkoxy or hydroxy, [2544]
R21 is hydrogen, [2545] R22 is 1-4C-fluoroalkoxy, [2546] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2547] R24 is hydrogen, [2548] Y is
--(CH.sub.2).sub.n--, [2549] n is 0 or 1, [2550] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2551] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2552] R41 is
1-4C-alkoxy or hydroxy, [2553] R42 is 1-4C-alkoxy or hydroxy,
[2554] R43 is 1-4C-alkoxy or hydroxy, [2555] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2556] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2557] R71 is 1-4C-alkoxy or hydroxy, [2558]
R72 is 1-4C-alkoxy or hydroxy, [2559] R73 is 1-4C-alkoxy or
hydroxy, [2560] R8 is hydrogen, [2561] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2562] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2563] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2564] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2565] R11 is 1-4C-alkoxy or hydroxy, [2566]
R21 is hydrogen, [2567] R22 is 1-4C-alkoxy, [2568] R23 is halogen,
[2569] R24 is hydrogen, [2570] Y is --(CH.sub.2).sub.n--, [2571] n
is 0 or 1, [2572] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2573] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2574] R41 is 1-4C-alkoxy or hydroxy, [2575]
R42 is 1-4C-alkoxy or hydroxy, [2576] R43 is 1-4C-alkoxy or
hydroxy, [2577] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2578] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2579] R71 is
1-4C-alkoxy or hydroxy, [2580] R72 is 1-4C-alkoxy or hydroxy,
[2581] R73 is 1-4C-alkoxy or hydroxy, [2582] R8 is hydrogen, [2583]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2584] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2585] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2586] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2587] R11 is 1-4C-alkoxy or hydroxy, [2588]
R21 is hydrogen, [2589] R22 is 1-4C-alkyl, [2590] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2591] R24 is hydrogen, [2592] Y is --(CH.sub.2).sub.n--, [2593] n
is 0 or 1, [2594] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2595] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2596] R41 is 1-4C-alkoxy or hydroxy, [2597]
R42 is 1-4C-alkoxy or hydroxy, [2598] R43 is 1-4C-alkoxy or
hydroxy, [2599] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2600] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2601] R71 is
1-4C-alkoxy or hydroxy, [2602] R72 is 1-4C-alkoxy or hydroxy,
[2603] R73 is 1-4C-alkoxy or hydroxy, [2604] R8 is hydrogen, [2605]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2606] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2607] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2608] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2609] R11 is 1-4C-alkoxy or hydroxy, [2610]
R21 and R22 combine to form a group --O--CH.sub.2--O--, [2611] R23
is hydrogen, [2612] R24 is hydrogen, [2613] Y is
--(CH.sub.2).sub.n--, [2614] n is 0 or 1, [2615] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2616] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2617] R41 is
1-4C-alkoxy or hydroxy, [2618] R42 is 1-4C-alkoxy or hydroxy,
[2619] R43 is 1-4C-alkoxy or hydroxy, [2620] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2621] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2622] R71 is 1-4C-alkoxy or hydroxy, [2623]
R72 is 1-4C-alkoxy or hydroxy, [2624] R73 is 1-4C-alkoxy or
hydroxy, [2625] R8 is hydrogen, [2626] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, which is
optionally substituted by R92, [2627] R91 is 1-4C-alkoxy or
hydroxy, [2628] R92 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[2629] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2630] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2631] R11 is 1-4C-alkoxy or hydroxy, [2632]
R21 is hydrogen, [2633] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2634] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2635] R23 is halogen, [2636] R24 is hydrogen, [2637] Y is
--(CH.sub.2).sub.n--, [2638] n is 0 or 1, [2639] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2640] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2641] R41 is
1-4C-alkoxy or hydroxy, [2642] R42 is 1-4C-alkoxy or hydroxy,
[2643] R43 is 1-4C-alkoxy or hydroxy, [2644] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2645] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2646] R71 is 1-4C-alkoxy or hydroxy, [2647]
R72 is 1-4C-alkoxy or hydroxy, [2648] R73 is 1-4C-alkoxy or
hydroxy, [2649] R8 is hydrogen, [2650] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2651] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2652] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2653] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2654] R11 is 1-4C-alkoxy or hydroxy, [2655]
R21 is hydrogen, [2656] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2657] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2658] R23 and R24 are hydrogen, [2659] Y is --(CH.sub.2).sub.n--,
[2660] n is 0 or 1, [2661] R3 is a 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom, said heterocyclic ring being optionally substituted by
R4, or a 3-6C-cycloalkyl group substituted by R6, [2662] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2663] R41 is 1-4C-alkoxy or hydroxy, [2664]
R42 is 1-4C-alkoxy or hydroxy, [2665] R43 is 1-4C-alkoxy or
hydroxy, [2666] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2667] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2668] R71 is
1-4C-alkoxy or hydroxy, [2669] R72 is 1-4C-alkoxy or hydroxy,
[2670] R73 is 1-4C-alkoxy or hydroxy, [2671] R8 is hydrogen, [2672]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2673] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2674] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2675] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2676] R11 is 1-4C-alkoxy or hydroxy, [2677]
R21 is hydrogen, [2678] R22 is fluorine, [2679] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2680] R24 is hydrogen, [2681] Y is --(CH.sub.2).sub.n--, [2682] n
is 0 or 1, [2683] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2684] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2685] R41 is 1-4C-alkoxy or hydroxy, [2686]
R42 is 1-4C-alkoxy or hydroxy, [2687] R43 is 1-4C-alkoxy or
hydroxy, [2688] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2689] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2690] R71 is
1-4C-alkoxy or hydroxy, [2691] R72 is 1-4C-alkoxy or hydroxy,
[2692] R73 is 1-4C-alkoxy or hydroxy, [2693] R8 is hydrogen, [2694]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2695] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2696] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2697] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2698] R11 is 1-4C-alkoxy or hydroxy, [2699]
R21 is hydrogen, [2700] R22 is methoxy, [2701] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2702] R24 is hydrogen, [2703] Y is --(CH.sub.2).sub.n--, [2704] n
is 0 or 1, [2705] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2706] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2707] R41 is 1-4C-alkoxy or hydroxy, [2708]
R42 is 1-4C-alkoxy or hydroxy, [2709] R43 is 1-4C-alkoxy or
hydroxy, [2710] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2711] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2712] R71 is
1-4C-alkoxy or hydroxy, [2713] R72 is 1-4C-alkoxy or hydroxy,
[2714] R73 is 1-4C-alkoxy or hydroxy, [2715] R8 is hydrogen, [2716]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2717] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2718] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2719] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2720] R11 is 1-4C-alkoxy or hydroxy, [2721]
R21 is hydrogen, [2722] R22 is methyl, [2723] R23 is hydrogen,
halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy,
[2724] R24 is hydrogen, [2725] Y is --(CH.sub.2).sub.n--, [2726] n
is 0 or 1, [2727] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2728] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2729] R41 is 1-4C-alkoxy or hydroxy, [2730]
R42 is 1-4C-alkoxy or hydroxy, [2731] R43 is 1-4C-alkoxy or
hydroxy, [2732] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2733] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2734] R71 is
1-4C-alkoxy or hydroxy, [2735] R72 is 1-4C-alkoxy or hydroxy,
[2736] R73 is 1-4C-alkoxy or hydroxy, [2737] R8 is hydrogen, [2738]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2739] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2740] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2741] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2742] R11 is 1-4C-alkoxy or hydroxy, [2743]
R21 is hydrogen, [2744] R22 is methylcarbonyl, [2745] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [2746] R24 is hydrogen, [2747] Y is
--(CH.sub.2).sub.n--, [2748] n is 0 or 1, [2749] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2750] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2751] R41 is
1-4C-alkoxy or hydroxy, [2752] R42 is 1-4C-alkoxy or hydroxy,
[2753] R43 is 1-4C-alkoxy or hydroxy, [2754] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2755] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2756] R71 is 1-4C-alkoxy or hydroxy, [2757]
R72 is 1-4C-alkoxy or hydroxy, [2758] R73 is 1-4C-alkoxy or
hydroxy, [2759] R8 is hydrogen, [2760] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2761] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2762] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2763] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2764] R11 is 1-4C-alkoxy or hydroxy, [2765]
R21 is hydrogen, [2766] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2767] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2768] R23 is fluorine, [2769] R24 is hydrogen, [2770] Y is
--(CH.sub.2).sub.n--, [2771] n is 0 or 1, [2772] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2773] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2774] R41 is
1-4C-alkoxy or hydroxy, [2775] R42 is 1-4C-alkoxy or hydroxy,
[2776] R43 is 1-4C-alkoxy or hydroxy, [2777] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2778] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2779] R71 is 1-4C-alkoxy or hydroxy, [2780]
R72 is 1-4C-alkoxy or hydroxy, [2781] R73 is 1-4C-alkoxy or
hydroxy, [2782] R8 is hydrogen, [2783] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2784] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2785] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2786] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2787] R11 is 1-4C-alkoxy or hydroxy, [2788]
R21 is hydrogen, [2789] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2790] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2791] R23 is methoxy, [2792] R24 is hydrogen, [2793] Y is
--(CH.sub.2).sub.n--, [2794] n is 0 or 1, [2795] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2796] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2797] R41 is
1-4C-alkoxy or hydroxy, [2798] R42 is 1-4C-alkoxy or hydroxy,
[2799] R43 is 1-4C-alkoxy or hydroxy, [2800] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2801] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2802] R71 is 1-4C-alkoxy or hydroxy, [2803]
R72 is 1-4C-alkoxy or hydroxy, [2804] R73 is 1-4C-alkoxy or
hydroxy, [2805] R8 is hydrogen, [2806] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2807] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2808] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2809] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2810] R11 is 1-4C-alkoxy or hydroxy, [2811]
R21 is hydrogen, [2812] R22 is methoxy, [2813] R23 is fluorine,
[2814] R24 is hydrogen, [2815] Y is --(CH.sub.2).sub.n--, [2816] n
is 0 or 1, [2817] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2818] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2819] R41 is 1-4C-alkoxy or hydroxy, [2820]
R42 is 1-4C-alkoxy or hydroxy, [2821] R43 is 1-4C-alkoxy or
hydroxy, [2822] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2823] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2824] R71 is
1-4C-alkoxy or hydroxy, [2825] R72 is 1-4C-alkoxy or hydroxy,
[2826] R73 is 1-4C-alkoxy or hydroxy, [2827] R8 is hydrogen, [2828]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2829] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2830] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2831] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2832] R11 is 1-4C-alkoxy or hydroxy, [2833]
R21 is hydrogen, [2834] R22 is fluorine, [2835] R23 is methoxy,
[2836] R24 is hydrogen, [2837] Y is --(CH.sub.2).sub.n--, [2838] n
is 0 or 1, [2839] R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being optionally substituted by R4, or a
3-6C-cycloalkyl group substituted by R6, [2840] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [2841] R41 is 1-4C-alkoxy or hydroxy, [2842]
R42 is 1-4C-alkoxy or hydroxy, [2843] R43 is 1-4C-alkoxy or
hydroxy, [2844] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2845] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2846] R71 is
1-4C-alkoxy or hydroxy, [2847] R72 is 1-4C-alkoxy or hydroxy,
[2848] R73 is 1-4C-alkoxy or hydroxy, [2849] R8 is hydrogen, [2850]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2851] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2852] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2853] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2854] R11 is 1-4C-alkoxy or hydroxy, [2855]
R21 is hydrogen, [2856] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2857] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2858] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2859] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2860] R24 is hydrogen, [2861] Y is
--(CH.sub.2).sub.n--, [2862] n is 0 or 1, [2863] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2864] R4 is --C(O)--H, [2865] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [2866] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2867] R71 is
1-4C-alkoxy or hydroxy, [2868] R72 is 1-4C-alkoxy or hydroxy,
[2869] R73 is 1-4C-alkoxy or hydroxy, [2870] R8 is hydrogen, [2871]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2872] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2873] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2874] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2875] R11 is 1-4C-alkoxy or hydroxy, [2876]
R21 is hydrogen, [2877] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2878] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2879] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2880] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2881] R24 is hydrogen, [2882] Y is
--(CH.sub.2).sub.n--, [2883] n is 0 or 1, [2884] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2885] R4 is --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41, [2886] R41 is
1-4C-alkoxy or hydroxy, [2887] R6 is --NH--C(O)--R7, --C(O)--NR8R9
or NH.sub.2, [2888] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [2889] R71 is 1-4C-alkoxy or hydroxy, [2890] R72 is
1-4C-alkoxy or hydroxy, [2891] R73 is 1-4C-alkoxy or hydroxy,
[2892] R8 is hydrogen, [2893] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [2894] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, or a stereoisomer of the compound or
the salt thereof.
[2895] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2896] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2897] R11 is 1-4C-alkoxy or hydroxy, [2898]
R21 is hydrogen, [2899] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2900] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2901] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2902] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2903] R24 is hydrogen, [2904] Y is
--(CH.sub.2).sub.n--, [2905] n is 0 or 1, [2906] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2907] R4 is --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by [2908] R42,
[2909] R42 is 1-4C-alkoxy or hydroxy, [2910] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [2911] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [2912] R71 is 1-4C-alkoxy or hydroxy, [2913]
R72 is 1-4C-alkoxy or hydroxy, [2914] R73 is 1-4C-alkoxy or
hydroxy, [2915] R8 is hydrogen, [2916] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [2917] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[2918] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2919] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2920] R11 is 1-4C-alkoxy or hydroxy, [2921]
R21 is hydrogen, [2922] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2923] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2924] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2925] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2926] R24 is hydrogen, [2927] Y is
--(CH.sub.2).sub.n--, [2928] n is 0 or 1, [2929] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2930] R4 is --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [2931] R43 is
1-4C-alkoxy or hydroxy, [2932] R6 is --NH--C(O)--R7, --C(O)--NR8R9
or NH.sub.2, [2933] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [2934] R71 is 1-4C-alkoxy or hydroxy, [2935] R72 is
1-4C-alkoxy or hydroxy, [2936] R73 is 1-4C-alkoxy or hydroxy,
[2937] R8 is hydrogen, [2938] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [2939] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, or a stereoisomer of the compound or
the salt thereof.
[2940] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2941] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2942] R11 is 1-4C-alkoxy or hydroxy, [2943]
R21 is hydrogen, [2944] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2945] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2946] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2947] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2948] R24 is hydrogen, [2949] Y is
--(CH.sub.2).sub.n--, [2950] n is 0 or 1, [2951] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2952] R4 is --C(O)--O-1-4C-alkyl, [2953] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [2954] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2955] R71 is
1-4C-alkoxy or hydroxy, [2956] R72 is 1-4C-alkoxy or hydroxy,
[2957] R73 is 1-4C-alkoxy or hydroxy, [2958] R8 is hydrogen, [2959]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [2960] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[2961] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2962] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2963] R11 is 1-4C-alkoxy or hydroxy, [2964]
R21 is hydrogen, [2965] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2966] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2967] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2968] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2969] R24 is hydrogen, [2970] Y is
--(CH.sub.2).sub.n--, [2971] n is 0 or 1, [2972] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2973] R4 is --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41, [2974] R41 is
1-4C-alkoxy, [2975] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or
NH.sub.2, [2976] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [2977] R71 is 1-4C-alkoxy or hydroxy, [2978] R72 is
1-4C-alkoxy or hydroxy, [2979] R73 is 1-4C-alkoxy or hydroxy,
[2980] R8 is hydrogen, [2981] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [2982] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, or a stereoisomer of the compound or
the salt thereof.
[2983] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [2984] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [2985] R11 is 1-4C-alkoxy or hydroxy, [2986]
R21 is hydrogen, [2987] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[2988] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[2989] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [2990] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [2991] R24 is hydrogen, [2992] Y is
--(CH.sub.2).sub.n--, [2993] n is 0 or 1, [2994] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [2995] R4 is --C(O)-2-4C-alkyl, wherein the
2-4C-alkyl group is optionally substituted by R41, [2996] R41 is
methoxy, [2997] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[2998] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [2999] R71 is
1-4C-alkoxy or hydroxy, [3000] R72 is 1-4C-alkoxy or hydroxy,
[3001] R73 is 1-4C-alkoxy or hydroxy, [3002] R8 is hydrogen, [3003]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3004] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3005] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3006] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3007] R11 is 1-4C-alkoxy or hydroxy, [3008]
R21 is hydrogen, [3009] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3010] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3011] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3012] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3013] R24 is hydrogen, [3014] Y is
--(CH.sub.2).sub.n--, [3015] n is 0 or 1, [3016] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3017] R4 is --C(O)-2-4C-alkyl, wherein the
2-4C-alkyl group is optionally substituted by R41, [3018] R41 is
hydroxy, [3019] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[3020] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3021] R71 is
1-4C-alkoxy or hydroxy, [3022] R72 is 1-4C-alkoxy or hydroxy,
[3023] R73 is 1-4C-alkoxy or hydroxy, [3024] R8 is hydrogen, [3025]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3026] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3027] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3028] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3029] R11 is 1-4C-alkoxy or hydroxy, [3030]
R21 is hydrogen, [3031] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3032] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3033] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3034] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3035] R24 is hydrogen, [3036] Y is
--(CH.sub.2).sub.n--, [3037] n is 0 or 1, [3038] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3039] R4 is --C(O)-cyclopropyl, wherein the
cyclopropyl group is optionally substituted by R42, [3040] R42 is
1-4C-alkoxy, [3041] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or
NH.sub.2, [3042] R7 is hydrogen, 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [3043] R71 is 1-4C-alkoxy or hydroxy, [3044] R72 is
1-4C-alkoxy or hydroxy, [3045] R73 is 1-4C-alkoxy or hydroxy,
[3046] R8 is hydrogen, [3047] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [3048] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, or a stereoisomer of the compound or
the salt thereof.
[3049] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3050] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3051] R11 is 1-4C-alkoxy or hydroxy, [3052]
R21 is hydrogen, [3053] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3054] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3055] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3056] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3057] R24 is hydrogen, [3058] Y is
--(CH.sub.2).sub.n--, [3059] n is 0 or 1, [3060] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3061] R4 is --C(O)-cyclopropyl, wherein the
cyclopropyl group is optionally substituted by R42, [3062] R42 is
methoxy, [3063] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[3064] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3065] R71 is
1-4C-alkoxy or hydroxy, [3066] R72 is 1-4C-alkoxy or hydroxy,
[3067] R73 is 1-4C-alkoxy or hydroxy, [3068] R8 is hydrogen, [3069]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3070] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3071] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3072] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3073] R11 is 1-4C-alkoxy or hydroxy, [3074]
R21 is hydrogen, [3075] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3076] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3077] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3078] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3079] R24 is hydrogen, [3080] Y is
--(CH.sub.2).sub.n--, [3081] n is 0 or 1, [3082] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3083] R4 is --C(O)-cyclopropyl, wherein the
cyclopropyl group is optionally substituted by R42, [3084] R42 is
hydroxy, [3085] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[3086] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3087] R71 is
1-4C-alkoxy or hydroxy, [3088] R72 is 1-4C-alkoxy or hydroxy,
[3089] R73 is 1-4C-alkoxy or hydroxy, [3090] R8 is hydrogen, [3091]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3092] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3093] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3094] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3095] R11 is 1-4C-alkoxy or hydroxy, [3096]
R21 is hydrogen, [3097] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3098] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3099] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3100] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3101] R24 is hydrogen, [3102] Y is
--(CH.sub.2).sub.n--, [3103] n is 0 or 1, [3104] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3105] R4 --C(O)--O-1-4C-alkyl, which is
optionally substituted by R43, [3106] R43 is 1-2C-alkoxy, [3107] R6
is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3108] R7 is
hydrogen, 1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3109] R71 is
1-4C-alkoxy or hydroxy, [3110] R72 is 1-4C-alkoxy or hydroxy,
[3111] R73 is 1-4C-alkoxy or hydroxy, [3112] R8 is hydrogen, [3113]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3114] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3115] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3116] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3117] R11 is 1-4C-alkoxy or hydroxy, [3118]
R21 is hydrogen, [3119] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3120] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3121] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3122] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3123] R24 is hydrogen, [3124] Y is
--(CH.sub.2).sub.n--, [3125] n is 0 or 1, [3126] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3127] R4 --C(O)--O-1-4C-alkyl, which is
optionally substituted by R43, [3128] R43 is methoxy, [3129] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3130] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3131] R71 is
1-4C-alkoxy or hydroxy, [3132] R72 is 1-4C-alkoxy or hydroxy,
[3133] R73 is 1-4C-alkoxy or hydroxy, [3134] R8 is hydrogen, [3135]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3136] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3137] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3138] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3139] R11 is 1-4C-alkoxy or hydroxy, [3140]
R21 is hydrogen, [3141] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3142] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3143] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3144] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3145] R24 is hydrogen, [3146] Y is
--(CH.sub.2).sub.n--, [3147] n is 0 or 1, [3148] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3149] R4 --C(O)--O-1-4C-alkyl, which is
optionally substituted by R43, [3150] R43 is hydroxy, [3151] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3152] R7 is hydrogen,
1-4C-alkyl, which is optionally substituted by R71,
3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3153] R71 is
1-4C-alkoxy or hydroxy, [3154] R72 is 1-4C-alkoxy or hydroxy,
[3155] R73 is 1-4C-alkoxy or hydroxy, [3156] R8 is hydrogen, [3157]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3158] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3159] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3160] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3161] R11 is 1-4C-alkoxy or hydroxy, [3162]
R21 is hydrogen, [3163] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3164] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3165] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3166] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3167] R24 is hydrogen, [3168] Y is
--(CH.sub.2).sub.n--, [3169] n is 0 or 1, [3170] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3171] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3172] R41 is
1-4C-alkoxy or hydroxy, [3173] R42 is 1-4C-alkoxy or hydroxy,
[3174] R43 is 1-4C-alkoxy or hydroxy, [3175] R6 is --NH--C(O)--R7,
[3176] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3177] R71 is
1-4C-alkoxy or hydroxy, [3178] R72 is 1-4C-alkoxy or hydroxy,
[3179] R73 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[3180] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3181] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3182] R11 is 1-4C-alkoxy or hydroxy, [3183]
R21 is hydrogen, [3184] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3185] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3186] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3187] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3188] R24 is hydrogen, [3189] Y is
--(CH.sub.2).sub.n--, [3190] n is 0 or 1, [3191] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3192] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3193] R41 is
1-4C-alkoxy or hydroxy, [3194] R42 is 1-4C-alkoxy or hydroxy,
[3195] R43 is 1-4C-alkoxy or hydroxy, [3196] R6 is --C(O)--NR8R9,
[3197] R8 is hydrogen, [3198] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [3199] R91 is 1-4C-alkoxy
or hydroxy, a salt thereof, or a stereoisomer of the compound or
the salt thereof.
[3200] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3201] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3202] R11 is 1-4C-alkoxy or hydroxy, [3203]
R21 is hydrogen, [3204] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3205] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3206] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3207] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3208] R24 is hydrogen, [3209] Y is
--(CH.sub.2).sub.n--, [3210] n is 0 or 1, [3211] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3212] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3213] R41 is
1-4C-alkoxy or hydroxy, [3214] R42 is 1-4C-alkoxy or hydroxy,
[3215] R43 is 1-4C-alkoxy or hydroxy, [3216] R6 is --NH--C(O)--R7,
[3217] R7 is 1-2C-alkyl, which is optionally substituted by R71,
[3218] R71 is 1-2C-alkoxy, [3219] R8 is hydrogen, [3220] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3221] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3222] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3223] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3224] R11 is 1-4C-alkoxy or hydroxy, [3225]
R21 is hydrogen, [3226] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3227] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3228] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3229] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3230] R24 is hydrogen, [3231] Y is
--(CH.sub.2).sub.n--, [3232] n is 0 or 1, [3233] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3234] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3235] R41 is
1-4C-alkoxy or hydroxy, [3236] R42 is 1-4C-alkoxy or hydroxy,
[3237] R43 is 1-4C-alkoxy or hydroxy, [3238] R6 is --NH--C(O)--R7,
[3239] R7 is 1-2C-alkyl, which is optionally substituted by R71,
[3240] R71 is hydroxy, [3241] R8 is hydrogen, [3242] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3243] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3244] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3245] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3246] R11 is 1-4C-alkoxy or hydroxy, [3247]
R21 is hydrogen, [3248] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3249] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3250] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3251] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3252] R24 is hydrogen, [3253] Y is
--(CH.sub.2).sub.n--, [3254] n is 0 or 1, [3255] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3256] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3257] R41 is
1-4C-alkoxy or hydroxy, [3258] R42 is 1-4C-alkoxy or hydroxy,
[3259] R43 is 1-4C-alkoxy or hydroxy, [3260] R6 is --NH--C(O)--R7,
[3261] R7 is cyclopropyl, which is optionally substituted by R72,
[3262] R72 is 1-2C-alkoxy, [3263] R8 is hydrogen, [3264] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3265] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3266] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3267] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3268] R11 is 1-4C-alkoxy or hydroxy, [3269]
R21 is hydrogen, [3270] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3271] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3272] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3273] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3274] R24 is hydrogen, [3275] Y is
--(CH.sub.2).sub.n--, [3276] n is 0 or 1, [3277] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3278] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3279] R41 is
1-4C-alkoxy or hydroxy, [3280] R42 is 1-4C-alkoxy or hydroxy,
[3281] R43 is 1-4C-alkoxy or hydroxy, [3282] R6 is --NH--C(O)--R7,
[3283] R7 is cyclopropyl, which is optionally substituted by R72,
[3284] R72 is hydroxy, [3285] R8 is hydrogen, [3286] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3287] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3288] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3289] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3290] R11 is 1-4C-alkoxy or hydroxy, [3291]
R21 is hydrogen, [3292] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3293] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3294] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3295] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3296] R24 is hydrogen, [3297] Y is
--(CH.sub.2).sub.n--, [3298] n is 0 or 1, [3299] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3300] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3301] R41 is
1-4C-alkoxy or hydroxy, [3302] R42 is 1-4C-alkoxy or hydroxy,
[3303] R43 is 1-4C-alkoxy or hydroxy, [3304] R6 is --NH--C(O)--R7,
[3305] R7 is 1-2C-alkoxy, [3306] R8 is hydrogen, [3307] R9 is
1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3308] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3309] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3310] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3311] R11 is 1-4C-alkoxy or hydroxy, [3312]
R21 is hydrogen, [3313] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3314] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3315] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3316] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3317] R24 is hydrogen, [3318] Y is
--(CH.sub.2).sub.n--, [3319] n is 0 or 1, [3320] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3321] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-2C-alkyl, wherein the
1-2C-alkyl group is optionally substituted by R43, [3322] R41 is
1-4C-alkoxy or hydroxy, [3323] R42 is 1-4C-alkoxy or hydroxy,
[3324] R43 is 1-4C-alkoxy or hydroxy, [3325] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [3326] R7 is 1-4C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-2C-alkoxy, which is optionally substituted
by R73, [3327] R71 is 1-4C-alkoxy or hydroxy, [3328] R72 is
1-4C-alkoxy or hydroxy, [3329] R73 is 1-4C-alkoxy or hydroxy,
[3330] R8 is hydrogen, [3331] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [3332] R91 is 1-4C-alkoxy
or hydroxy, salts thereof, and stereoisomers of the compounds and
the salts thereof.
[3333] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3334] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3335] R11 is 1-4C-alkoxy or hydroxy, [3336]
R21 is hydrogen, [3337] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3338] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3339] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3340] R24 is hydrogen, [3341] Y is
--(CH.sub.2).sub.n--, [3342] n is 0 or 1, [3343] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3344] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41, or
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, [3345] R41 is 1-4C-alkoxy or
hydroxy, [3346] R42 is 1-4C-alkoxy or hydroxy, [3347] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3348] R7 is 1-4C-alkyl,
which is optionally substituted by R71, or 3-6C-cycloalkyl, which
is optionally substituted by R72, [3349] R71 is 1-4C-alkoxy or
hydroxy, [3350] R72 is 1-4C-alkoxy or hydroxy, [3351] R8 is
hydrogen, [3352] R9 is 1-4C-alkyl, which is optionally substituted
by R91, or 3-6C-cycloalkyl, [3353] R91 is 1-4C-alkoxy or hydroxy,
salts thereof, and stereoisomers of the compounds and the salts
thereof.
[3354] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3355] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3356] R11 is 1-4C-alkoxy or hydroxy, [3357]
R21 is hydrogen, [3358] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3359] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3360] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3361] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3362] R24 is hydrogen, [3363] Y is
--(CH.sub.2).sub.n--, [3364] n is 0 or 1, [3365] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3366] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3367] R41 is
1-4C-alkoxy or hydroxy, [3368] R42 is 1-4C-alkoxy or hydroxy,
[3369] R43 is 1-4C-alkoxy or hydroxy, [3370] R6 is --NH--C(O)--R7
or --C(O)--NR8R9, [3371] R7 is hydrogen, 1-4C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, [3372] R71 is 1-4C-alkoxy or hydroxy, [3373] R72 is
1-4C-alkoxy or hydroxy, [3374] R73 is 1-4C-alkoxy or hydroxy,
[3375] R8 is hydrogen, [3376] R9 is 1-4C-alkyl, which is optionally
substituted by R91, or 3-6C-cycloalkyl, [3377] R91 is 1-4C-alkoxy
or hydroxy, salts thereof, and stereoisomers of the compounds and
the salts thereof.
[3378] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3379] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3380] R11 is 1-4C-alkoxy or hydroxy, [3381]
R21 is hydrogen, [3382] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3383] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3384] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3385] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3386] R24 is hydrogen, [3387] Y is
--(CH.sub.2).sub.n--, [3388] n is 0 or 1, [3389] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3390] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41, or
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by [3391] R42, [3392] R41 is 1-4C-alkoxy or
hydroxy, [3393] R42 is 1-4C-alkoxy or hydroxy, [3394] R6 is
--NH--C(O)--R7 or --C(O)--NR8R9, [3395] R7 is 1-4C-alkyl, which is
optionally substituted by R71, or 3-6C-cycloalkyl, which is
optionally substituted by R72, [3396] R71 is 1-4C-alkoxy or
hydroxy, [3397] R72 is 1-4C-alkoxy or hydroxy, [3398] R8 is
hydrogen, [3399] R9 is 1-4C-alkyl, which is optionally substituted
by R91, or 3-6C-cycloalkyl, [3400] R91 is 1-4C-alkoxy or hydroxy,
salts thereof, and stereoisomers of the compounds and the salts
thereof.
[3401] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3402] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3403] R11 is 1-4C-alkoxy or hydroxy, [3404]
R21 is hydrogen, [3405] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3406] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3407] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3408] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3409] R24 is hydrogen, [3410] Y is
--(CH.sub.2).sub.n--, [3411] n is 0 or 1, [3412] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3413] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3414] R41 is
1-4C-alkoxy or hydroxy, [3415] R42 is 1-4C-alkoxy or hydroxy,
[3416] R43 is 1-4C-alkoxy or hydroxy, [3417] R6 is --C(O)--NR8R9,
[3418] R8 is hydrogen, [3419] R9 is 1-2C-alkyl, which is optionally
substituted by R91, [3420] R91 is 1-2C-alkoxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[3421] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3422] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3423] R11 is 1-4C-alkoxy or hydroxy, [3424]
R21 is hydrogen, [3425] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3426] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3427] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3428] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3429] R24 is hydrogen, [3430] Y is
--(CH.sub.2).sub.n--, [3431] n is 0 or 1, [3432] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3433] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3434] R41 is
1-4C-alkoxy or hydroxy, [3435] R42 is 1-4C-alkoxy or hydroxy,
[3436] R43 is 1-4C-alkoxy or hydroxy, [3437] R6 is --C(O)--NR8R9,
[3438] R8 is hydrogen, [3439] R9 is 1-2C-alkyl, which is optionally
substituted by R91, [3440] R91 is hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[3441] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3442] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3443] R11 is 1-4C-alkoxy or hydroxy, [3444]
R21 is hydrogen, [3445] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3446] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3447] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3448] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3449] R24 is hydrogen, [3450] Y is
--(CH.sub.2).sub.n--, [3451] n is 0 or 1, [3452] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3453] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3454] R41 is
1-4C-alkoxy or hydroxy, [3455] R42 is 1-4C-alkoxy or hydroxy,
[3456] R43 is 1-4C-alkoxy or hydroxy, [3457] R6 is --C(O)--NR8R9,
[3458] R8 is hydrogen, [3459] R9 is cyclopropyl, a salt thereof, or
a stereoisomer of the compound or the salt thereof.
[3460] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3461] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3462] R11 is 1-4C-alkoxy or hydroxy, [3463]
R21 is hydrogen, [3464] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3465] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3466] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3467] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3468] R24 is hydrogen, [3469] Y is
--(CH.sub.2).sub.n--, [3470] n is 0 or 1, [3471] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, wherein R4, if present, is bonded to
said nitrogen atom, [3472] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3473] R41 is
1-4C-alkoxy or hydroxy, [3474] R42 is 1-4C-alkoxy or hydroxy,
[3475] R43 is 1-4C-alkoxy or hydroxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[3476] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3477] R1 is
--CH.sub.2-3-6C-cycloalkyl or 1-4C-alkyl which is optionally
substituted by R11, [3478] R11 is 1-4C-alkoxy or hydroxy, [3479]
R21 is hydrogen, [3480] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3481] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3482] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3483] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3484] R24 is hydrogen, [3485] Y is
--(CH.sub.2).sub.n--, [3486] n is 0 or 1, [3487] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
substituted by R4 at said nitrogen atom, [3488] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [3489] R41 is 1-4C-alkoxy or hydroxy, [3490]
R42 is 1-4C-alkoxy or hydroxy, [3491] R43 is 1-4C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[3492] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3493] R1 is
--CH.sub.2-3-4C-cycloalkyl or 2-4C-alkyl which is optionally
substituted by R11, [3494] R11 is 1-4C-alkoxy, [3495] R21 is
hydrogen, [3496] R22 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy,
hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl, [3497] or R21 and
R22 combine to form a group --O--CH.sub.2--O--, [3498] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [3499] or R22 and R23 combine to form a group
--O--CH.sub.2--O--, [3500] R24 is hydrogen, [3501] Y is
--(CH.sub.2).sub.n--, [3502] n is 0 or 1, [3503] R3 is a 4- to
6-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
substituted by R4 at said nitrogen atom, [3504] R4 is --C(O)--H,
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [3505] R41 is 1-4C-alkoxy or hydroxy, [3506]
R42 is 1-4C-alkoxy or hydroxy, [3507] R43 is 1-4C-alkoxy or
hydroxy, salts thereof, and stereoisomers of the compounds and the
salts thereof.
[3508] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3509] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3510] R21 is hydrogen, [3511] R22 is
hydrogen, [3512] R23 is hydrogen, [3513] R24 is hydrogen, [3514] Y
is --(CH.sub.2).sub.n--, [3515] n is 0, [3516] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3517] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl or --C(O)--O-1-4C-alkyl, [3518] R41 is hydroxy,
[3519] R6 is --NH--C(O)--R7 or NH.sub.2, [3520] R7 is 1-2C-alkyl,
which is optionally substituted by R71, cyclopropyl, which is
optionally substituted by R72, or 1-2C-alkoxy, which is optionally
substituted by R73, [3521] R71 is 1-2C-alkoxy or hydroxy, [3522]
R72 is hydroxy, [3523] R73 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3524] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3525] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3526] R21 is hydrogen, [3527] R22 is
hydrogen, [3528] R23 is 1-4C-alkoxy, [3529] R24 is hydrogen, [3530]
Y is --(CH.sub.2).sub.n--, [3531] n is 0, [3532] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3533] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein cyclopropyl group is optionally
substituted by R42, --C(O)--O-1-4C-alkyl, [3534] R41 is 1-2C-alkoxy
or hydroxy, [3535] R42 is hydroxy, [3536] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [3537] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [3538] R71 is 1-2C-alkoxy or
hydroxy, [3539] R72 is hydroxy, [3540] R8 is hydrogen, [3541] R9 is
1-2C-alkyl, which is optionally substituted by R91, or cyclopropyl,
[3542] R91 is 1-2C-alkoxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[3543] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3544] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3545] R21 is hydrogen, [3546] R22 is
halogen, [3547] R23 is 1-4C-alkoxy, [3548] R24 is hydrogen, [3549]
Y is --(CH.sub.2).sub.n--, [3550] n is 0, [3551] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4, or
a cyclohexyl group substituted by R6, [3552] R4 is
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclopropyl, wherein the cyclopropyl
group is optionally substituted by R42, or --C(O)--O-1-4C-alkyl,
[3553] R41 is 1-2C-alkoxy or hydroxy, [3554] R42 is hydroxy, [3555]
R6 is --NH--C(O)--R7 or NH.sub.2, [3556] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [3557] R71 is 1-2C-alkoxy or
hydroxy, [3558] R72 is hydroxy, a salt thereof, or a stereoisomer
of the compound or the salt thereof.
[3559] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3560] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3561] R21 is hydrogen, [3562] R22 is
--C(O)-1-4C-alkyl, [3563] R23 is hydrogen, [3564] R24 is hydrogen,
[3565] Y is --(CH.sub.2).sub.n--, [3566] n is 0, [3567] R3 is a
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[3568] R4 is --C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is
optionally substituted by R41, [3569] R41 is 1-2C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[3570] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3571] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3572] R21 is hydrogen, [3573] R22 is
halogen, [3574] R23 is hydrogen, [3575] R24 is hydrogen, [3576] Y
is --(CH.sub.2).sub.n--, [3577] n is 0, [3578] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3579] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41, or
--C(O)--O-1-4C-alkyl, [3580] R41 is 1-2C-alkoxy or hydroxy, [3581]
R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3582] R7 is
1-2C-alkyl, which is optionally substituted by R71, or 1-4C-alkoxy,
[3583] R71 is 1-2C-alkoxy or hydroxy, [3584] R8 is hydrogen, [3585]
R9 is 1-2C-alkyl, which is optionally substituted by R91, or
cyclopropyl, [3586] R91 is 1-2C-alkoxy, a salt thereof, or a
stereoisomer of the compound or the salt thereof.
[3587] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3588] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3589] R21 is hydrogen, [3590] R22 is
1-4C-alkoxy, [3591] R23 is hydrogen, [3592] R24 is hydrogen, [3593]
Y is --(CH.sub.2).sub.n--, [3594] n is 0, [3595] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3596] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein the cyclopropyl group is optionally
substituted by R42, or --C(O)--O-1-4C-alkyl, [3597] R41 is
1-2C-alkoxy or hydroxy, [3598] R42 is hydroxy, [3599] R6 is
--NH--C(O)--R7 or NH.sub.2, [3600] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [3601] R71 is 1-2C-alkoxy or
hydroxy, [3602] R72 is hydroxy, a salt thereof, or a stereoisomer
of the compound or the salt thereof.
[3603] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3604] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3605] R21 is hydrogen, [3606] R22 is
1-4C-fluoroalkoxy, [3607] R23 is hydrogen, [3608] R24 is hydrogen,
[3609] Y is --(CH.sub.2).sub.n--, [3610] n is 0, [3611] R3 is a
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4, or
a cyclohexyl group substituted by R6, [3612] R4 is
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclopropyl, wherein the cyclopropyl
group is optionally substituted by R42, or --C(O)--O-1-4C-alkyl,
[3613] R41 is 1-2C-alkoxy or hydroxy, [3614] R42 is hydroxy, [3615]
R6 is --NH--C(O)--R7 or NH.sub.2, [3616] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [3617] R71 is 1-2C-alkoxy or
hydroxy, [3618] R72 is hydroxy, a salt thereof, or a stereoisomer
of the compound or the salt thereof.
[3619] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3620] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3621] R21 is hydrogen, [3622] R22 is
1-4C-alkoxy, [3623] R23 is halogen, [3624] R24 is hydrogen, [3625]
Y is --(CH.sub.2).sub.n--, [3626] n is 0, [3627] R3 is a 5- to
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[3628] R4 is --C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is
optionally substituted by R41, or --C(O)--O-1-4C-alkyl, [3629] R41
is 1-2C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[3630] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3631] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3632] R21 is hydrogen, [3633] R22 is
1-4C-alkyl, [3634] R23 is hydrogen, [3635] R24 is hydrogen, [3636]
Y is --(CH.sub.2).sub.n--, [3637] n is 0, [3638] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3639] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein the cyclopropyl group is optionally
substituted by R42, or --C(O)--O-1-4C-alkyl, [3640] R41 is
1-2C-alkoxy or hydroxy, [3641] R42 is hydroxy, [3642] R6 is
--NH--C(O)--R7, or NH.sub.2, [3643] R7 is 1-2C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [3644] R71 is 1-2C-alkoxy or
hydroxy, [3645] R72 is hydroxy, a salt thereof, or a stereoisomer
of the compound or the salt thereof.
[3646] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3647] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3648] R21 and R22 combine to form a
group --O--CH.sub.2--O--, [3649] R23 is hydrogen, [3650] R24 is
hydrogen, [3651] Y is --(CH.sub.2).sub.n--, [3652] n is 0 or 1,
[3653] R3 is a 4- to 6-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3654] R4 is --C(O)--H,
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclohexyl, wherein the cyclohexyl group
is optionally substituted by R42, or --C(O)--O-1-4C-alkyl, [3655]
R41 is 1-2C-alkoxy or hydroxy, [3656] R42 is hydroxy, [3657] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3658] R7 is 1-2C-alkyl,
which is optionally substituted by R71, cyclopropyl, which is
optionally substituted by R72, or 1-4C-alkoxy, [3659] R71 is
1-2C-alkoxy or hydroxy, [3660] R72 is hydroxy, [3661] R8 is
hydrogen, [3662] R9 is 1-2C-alkyl, which is optionally substituted
by R91, or cyclopropyl, [3663] R91 is 1-2C-alkoxy or hydroxy, a
salt thereof, or a stereoisomer of the compound or the salt
thereof.
[3664] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3665] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3666] R21 and R22 combine to form a
group --O--CH.sub.2--O--, [3667] R23 is hydrogen, [3668] R24 is
hydrogen, [3669] Y is --(CH.sub.2).sub.n--, [3670] n is 0, [3671]
R3 is a 4- to 6-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a cyclohexyl group
substituted by R6, [3672] R4 is --C(O)--H, --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41,
--C(O)-cyclopropyl, wherein the cyclopropyl group is optionally
substituted by R42, or --C(O)--O-1-4C-alkyl, [3673] R41 is
1-2C-alkoxy or hydroxy, [3674] R42 is hydroxy, [3675] R6 is
--NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2, [3676] R7 is 1-2C-alkyl,
which is optionally substituted by R71, cyclopropyl, which is
optionally substituted by R72, or 1-4C-alkoxy, [3677] R71 is
1-2C-alkoxy or hydroxy, [3678] R72 is hydroxy, [3679] R8 is
hydrogen, [3680] R9 is 1-2C-alkyl, which is optionally substituted
by R91, or cyclopropyl, [3681] R91 is 1-2C-alkoxy or hydroxy, a
salt thereof, or a stereoisomer of the compound or the salt
thereof.
[3682] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3683] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3684] R21 and R22 combine to form a
group --O--CH.sub.2--O--, [3685] R23 is hydrogen, [3686] R24 is
hydrogen, [3687] Y is --(CH.sub.2).sub.n--, [3688] n is 1, [3689]
R3 is a 5- to 6-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, [3690] R4 is --C(O)--H,
--C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is optionally
substituted by R41, --C(O)-cyclopropyl, wherein the cyclopropyl
group is optionally substituted by R42, or --C(O)--O-1-4C-alkyl,
[3691] R41 is 1-2C-alkoxy or hydroxy, [3692] R42 is hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
[3693] R1 is --CH.sub.2-3-4C-cycloalkyl, [3694] R21 is hydrogen,
[3695] R22 is halogen, [3696] R23 is 1-4C-alkoxy, [3697] R24 is
hydrogen, [3698] Y is --(CH.sub.2).sub.n--, [3699] n is 0 or 1,
[3700] R3 is a 5- to 6-membered saturated heterocyclic ring
containing one nitrogen atom, said heterocyclic ring being
substituted by R4, [3701] R4 is --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41, [3702] R41 is
1-4C-alkoxy or hydroxy, salts thereof, and stereoisomers of the
compounds and the salts thereof.
[3703] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3704] R1 is
--CH.sub.2-3-4C-cycloalkyl, [3705] R21 is hydrogen, [3706] R22 is
hydrogen, [3707] R23 is halogen, [3708] R24 is hydrogen, [3709] Y
is --(CH.sub.2).sub.n--, [3710] n is 0, [3711] R3 is a 6-membered
saturated heterocyclic ring containing one nitrogen atom, said
heterocyclic ring being optionally substituted by R4, or a
cyclohexyl group substituted by R6, [3712] R4 is --C(O)-1-2C-alkyl,
wherein the 1-2C-alkyl group is optionally substituted by R41, or
--C(O)--O-1-4C-alkyl, [3713] R41 is 1-2C-alkoxy or hydroxy, [3714]
R6 is --NH--C(O)--R7 or NH.sub.2, [3715] R7 is 1-2C-alkyl, which is
optionally substituted by R71, cyclopropyl, which is optionally
substituted by R72, or 1-4C-alkoxy, [3716] R71 is 1-2C-alkoxy or
hydroxy, [3717] R72 is hydroxy, a salt thereof, or a stereoisomer
of the compound or the salt thereof.
[3718] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3719] R1 1-4C-alkyl which is
optionally substituted by R11, [3720] R11 is 1-4C-alkoxy or
hydroxy, [3721] R21 is hydrogen, [3722] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [3723] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [3724] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [3725] or R22 and R23
combine to form a group --O--CH.sub.2--O-- [3726] R24 is hydrogen,
[3727] Y is --(CH.sub.2).sub.n--, [3728] n is 0 or 1, [3729] R3 is
a 6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[3730] R4 is --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, [3731] R41 is 1-2C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[3732] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3733] R1 1-4C-alkyl which is
optionally substituted by R11, [3734] R11 is 1-4C-alkoxy or
hydroxy, [3735] R21 is hydrogen, [3736] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [3737] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [3738] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [3739] or R22 and R23
combine to form a group --O--CH.sub.2--O-- [3740] R24 is hydrogen,
[3741] Y is --(CH.sub.2).sub.n--, [3742] n is 0, [3743] R3 is a
6-membered saturated heterocyclic ring containing one nitrogen
atom, said heterocyclic ring being optionally substituted by R4,
[3744] R4 is --C(O)-1-2C-alkyl, wherein the 1-2C-alkyl group is
optionally substituted by R41, [3745] R41 is 1-2C-alkoxy or
hydroxy, a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[3746] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3747] R1 1-4C-alkyl which is
optionally substituted by R11, [3748] R11 is 1-4C-alkoxy or
hydroxy, [3749] R21 is hydrogen, [3750] R22 is hydrogen, halogen,
1-4C-alkyl, 1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or
--C(O)-1-4C-alkyl, [3751] or R21 and R22 combine to form a group
--O--CH.sub.2--O--, [3752] R23 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy or 1-4C-fluoroalkoxy, [3753] or R22 and R23
combine to form a group --O--CH.sub.2--O-- [3754] R24 is hydrogen,
[3755] Y is --(CH.sub.2).sub.n--, [3756] n is 0 or 1, [3757] R3 is
a 4- to 7-membered saturated heterocyclic ring containing one
nitrogen atom and optionally one oxygen atom, said heterocyclic
ring being optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3758] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3759] R41 is
1-4C-alkoxy or hydroxy, [3760] R42 is 1-4C-alkoxy or hydroxy,
[3761] R43 is 1-4C-alkoxy or hydroxy, [3762] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [3763] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [3764] R71 is 1-4C-alkoxy or hydroxy, [3765]
R72 is 1-4C-alkoxy or hydroxy, [3766] R73 is 1-4C-alkoxy or
hydroxy, [3767] R8 is hydrogen, [3768] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [3769] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[3770] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3771] R1 3-4C-alkyl, [3772] R21
is hydrogen, [3773] R22 is hydrogen, halogen, 1-4C-alkyl,
1-4C-alkoxy, hydroxy, 1-4C-fluoroalkoxy or --C(O)-1-4C-alkyl,
[3774] or R21 and R22 combine to form a group --O--CH.sub.2--O--,
[3775] R23 is hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy
or 1-4C-fluoroalkoxy, [3776] or R22 and R23 combine to form a group
--O--CH.sub.2--O-- [3777] R24 is hydrogen, [3778] Y is
--(CH.sub.2).sub.n--, [3779] n is 0 or 1, [3780] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3781] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3782] R41 is
1-4C-alkoxy or hydroxy, [3783] R42 is 1-4C-alkoxy or hydroxy,
[3784] R43 is 1-4C-alkoxy or hydroxy, [3785] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [3786] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [3787] R71 is 1-4C-alkoxy or hydroxy, [3788]
R72 is 1-4C-alkoxy or hydroxy, [3789] R73 is 1-4C-alkoxy or
hydroxy, [3790] R8 is hydrogen, [3791] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [3792] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[3793] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3794] R1 3-4C-alkyl, [3795] R21
and R22 combine to form a group --O--CH.sub.2--O--, [3796] R23 is
hydrogen, halogen, 1-4C-alkyl, 1-4C-alkoxy, hydroxy or
1-4C-fluoroalkoxy, [3797] R24 is hydrogen, [3798] Y is
--(CH.sub.2).sub.n--, [3799] n is 0 or 1, [3800] R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4, or a 3-6C-cycloalkyl group
substituted by R6, [3801] R4 is --C(O)--H, --C(O)-1-4C-alkyl,
wherein the 1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, [3802] R41 is
1-4C-alkoxy or hydroxy, [3803] R42 is 1-4C-alkoxy or hydroxy,
[3804] R43 is 1-4C-alkoxy or hydroxy, [3805] R6 is --NH--C(O)--R7,
--C(O)--NR8R9 or NH.sub.2, [3806] R7 is hydrogen, 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, [3807] R71 is 1-4C-alkoxy or hydroxy, [3808]
R72 is 1-4C-alkoxy or hydroxy, [3809] R73 is 1-4C-alkoxy or
hydroxy, [3810] R8 is hydrogen, [3811] R9 is 1-4C-alkyl, which is
optionally substituted by R91, or 3-6C-cycloalkyl, [3812] R91 is
1-4C-alkoxy or hydroxy, a salt thereof, or a stereoisomer of the
compound or the salt thereof.
[3813] In a further preferred embodiment, the invention relates to
compounds of formula (I), wherein [3814] R1 3-4C-alkyl, [3815] R21
and R22 combine to form a group --O--CH.sub.2--O--, [3816] R23 is
hydrogen, [3817] R24 is hydrogen, [3818] Y is --(CH.sub.2).sub.n--,
[3819] n is 0 or 1, [3820] R3 is a 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom, said heterocyclic ring being optionally substituted by
R4, or a 3-6C-cycloalkyl group substituted by R6, [3821] R4 is
--C(O)--H, --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, [3822] R41 is 1-4C-alkoxy or hydroxy, [3823]
R42 is 1-4C-alkoxy or hydroxy, [3824] R43 is 1-4C-alkoxy or
hydroxy, [3825] R6 is --NH--C(O)--R7, --C(O)--NR8R9 or NH.sub.2,
[3826] R7 is hydrogen, 1-4C-alkyl, which is optionally substituted
by R71, 3-6C-cycloalkyl, which is optionally substituted by R72, or
1-4C-alkoxy, which is optionally substituted by R73, [3827] R71 is
1-4C-alkoxy or hydroxy, [3828] R72 is 1-4C-alkoxy or hydroxy,
[3829] R73 is 1-4C-alkoxy or hydroxy, [3830] R8 is hydrogen, [3831]
R9 is 1-4C-alkyl, which is optionally substituted by R91, or
3-6C-cycloalkyl, [3832] R91 is 1-4C-alkoxy or hydroxy, a salt
thereof, or a stereoisomer of the compound or the salt thereof.
In a further preferred embodiment, the invention relates to
compounds of formula (I), selected from
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-propionyl-piperidin-4-yl)-am id;
4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-formyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]amide;
(R)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid ((S)-1-formyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-pyrrolidin-3-yl]amide;
(S)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-formyl-piperidin-4-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-acetyl-piperidin-4-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[141-cyclopropyl-methanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-ylmethyl]-amide;
4-[({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidin-7-yl]-methanoyl}-amino)-methyl]-piperidine-1-carboxylic
acid ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-piperidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-propionyl-piperidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-acetyl)piperidin-3-ylmethyl]-amide;
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)piperidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-pyrrolidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-acetyl)-pyrrolidin-3-ylmethyl]-amide;
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (4-formyl-morpholin-2-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-propionyl-morpholin-2-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetyl)-morpholin-2-ylmethyl]-amide;
2-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-acetyl-azetidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-propionyl-azetidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-ethanoyl)-azetidin-3-yl]amide;
3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-azetidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-piperidin-4-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-({1-[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
in-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amideter;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-propionylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-acetyl-piperidin-4-yl)-amide;
4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbony-
l]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-({1-[4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-(2-methoxy-acetyl)piperidin-4-yl]amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-(2-methoxy-acetyl)-pyrrolidin-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
bonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-formyl-piperidin-4-yl)-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-3-yl)-amide;
3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-(2-methoxy-acetyl)piperidin-3-yl]amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-[4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]-
pyrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid ethyl
ester;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{(R)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{(S)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-ylmethyl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-acetyl)-piperidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-piperidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-acetyl)-pyrrolidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-hydroxy-acetyl)-morpholin-2-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionyl)-morpholin-2-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-azetidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-azetidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-pyrrolidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-pyrrolidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
(4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
(1-acetyl-piperidin-4-yl)-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
[1-(2-hydroxy-acetyl)-piperidin-4-yl]-amide;
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide;
[3833] a salt thereof, or a stereoisomer of the compound or the
salt thereof.
In a further preferred embodiment, the invention relates to
compounds of formula (I), selected from
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amid;
4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-formyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]amide;
(R)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid ((S)-1-formyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-pyrrolidin-3-yl]-amide;
(S)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-formyl-piperidin-4-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-acetyl-piperidin-4-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[141-cyclopropyl-methanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-ylmethyl]-amide;
4-[({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidin-7-yl]-methanoyl}-amino)-methyl]-piperidine-1-carboxylic
acid ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-piperidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-propionyl-piperidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-acetyl)piperidin-3-ylmethyl]-amide;
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-piperidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-formyl-pyrrolidin-3-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-methoxy-acetyl)-pyrrolidin-3-ylmethyl]-amide;
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (4-formyl-morpholin-2-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-propionyl-morpholin-2-ylmethyl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetyl)-morpholin-2-ylmethyl]-amide;
2-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid
ethyl ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carboxylic acid (1-acetyl-azetidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-propionyl-azetidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-ethanoyl)-azetidin-3-yl]-amide;
3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-azetidine-1-carboxylic acid ethyl
ester;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-formyl-piperidin-4-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-({1-[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
in-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amideter;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-propionylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-acetyl-piperidin-4-yl)-amide;
4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbony-
l]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]amide;
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide;
4-({1-[4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-(2-methoxy-acetyl)piperidin-4-yl]amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-(2-methoxy-acetyl)-pyrrolidin-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
bonyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide;
4-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-formyl-piperidin-4-yl)-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-3-yl)-amide;
3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-(2-methoxy-acetyl)piperidin-3-yl]amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide;
(R)-3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)-cyclohexyl]-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide;
cis-[4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]-
pyrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid ethyl
ester;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide;
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide;
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{(R)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{(S)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)piperidin-4-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-ylmethyl}-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-acetyl)piperidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-piperidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-(2-hydroxy-acetyl)-pyrrolidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-hydroxy-acetyl)morpholin-2-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionyl)-morpholin-2-ylmethyl]-amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-azetidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-azetidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]amide;
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid [4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-pyrrolidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide;
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-piperidin-3-yl]-amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-pyrrolidin-3-yl]amide;
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide;
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide;
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide;
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide;
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide;
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide;
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]amide;
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid
(4-cyclopropylcarbamoyl-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide;
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide;
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
(4-cyclopropylcarbamoyl-cyclohexyl)-amide;
[3834] a salt thereof, or a stereoisomer of the compound or the
salt thereof.
[3835] It is to be understood that the invention covers all
combinations of substituent groups referred to hereinabove. In
particular, the invention covers all combinations of preferred
groups described hereinabove.
[3836] Salts of the compounds according to the invention and the
stereoisomers thereof include all inorganic and organic acid
addition salts and salts with bases, especially all
pharmaceutically acceptable inorganic and organic acid addition
salts and salts with bases, particularly all pharmaceutically
acceptable inorganic and organic acid addition salts and salts with
bases customarily used in pharmacy.
[3837] Examples of acid addition salts include, but are not limited
to, hydrochlorides, hydrobromides, phosphates, nitrates, sulfates,
acetates, trifluoroacetates, citrates, gluconates including
D-gluconates and L-gluconates, glucuronates including
D-glucuronates and L-glucuronates, benzoates,
2-(4-hydroxybenzoyl)benzoates, butyrates, salicylates,
sulfosalicylates, maleates, laurates, malates including L-malates
and D-malates, lactates including L-lactates and D-lactates,
fumarates, succinates, oxalates, tartarates including L-tartarates,
D-tartarates and meso-tartarates, stearates, benzenesulfonates
(besilates), toluenesulfonates (tosilates), methanesulfonates
(mesilates), laurylsulfonates, 3-hydroxy-2-naphthoates,
lactobionates (salts of 4-O-beta-D-galactopyranosyl-D-gluconic
acid), galactarates, embonates and ascorbates.
[3838] Examples of salts with bases include, but are not limited
to, lithium, sodium, potassium, calcium, aluminum, magnesium,
titanium, ammonium, meglumine and guanidinium salts.
[3839] The salts include water-insoluble and, particularly,
water-soluble salts.
[3840] The compounds according to the invention, the salts thereof,
the N-oxides of the compounds and the salts thereof and the
stereoisomers of the compounds, salts, N-oxides of the compounds
and N-oxides of the salts thereof may contain, e.g. when isolated
in crystalline form, varying amounts of solvents. Included within
the scope of the invention are, therefore, all solvates of the
compounds of formula (I), the salts thereof, the N-oxides of the
compounds and the salts thereof and the stereoisomers of the
compounds, salts, N-oxides of the compounds and N-oxides of the
salts thereof. Hydrates are a preferred example of said
solvates.
[3841] The compounds according to the invention and the salts
thereof, the N-oxides of the compounds and the salts thereof
include stereoisomers.
[3842] Examples of stereoisomers include, but are not limited to,
compounds of formula (I) wherein R3 is a 3-6C-cycloalkyl group
substituted by R6. Stereoisomers of one exemplified compound of
formula (I) wherein R3 is a 3-6C-cycloalkyl group substituted by R6
are shown below (cis/trans stereoisomers):
##STR00003##
[3843] Further examples of stereoisomers include, but are not
limited to, compounds of formula (I) wherein R3 is a 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, said heterocyclic ring being
optionally substituted by R4 and wherein said heterocyclic ring
contains a stereogenic center. Stereoisomers of an exemplified
compound of formula (I) wherein R3 is a 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom, said heterocyclic ring being optionally substituted by
R4 and said heterocyclic ring containing a stereogenic center are
shown below:
##STR00004##
[3844] Stereoisomers of a further exemplified compound of formula
(I) wherein R3 is a 4- to 7-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom, said
heterocyclic ring being optionally substituted by R4 and said
heterocyclic ring containing a stereogenic center are shown
below:
##STR00005##
[3845] Stereoisomers of a further exemplified compound of formula
(I) wherein R3 is a 4- to 7-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom, said
heterocyclic ring being optionally substituted by R4 and said
heterocyclic ring containing a stereogenic center are shown
below:
##STR00006##
[3846] Further examples of stereoisomers include, but are not
limited to, compounds of formula (I) wherein R4 is a group having a
stereogenic center, such as a group --C(O)--CH(CH.sub.3)--OH.
Further examples of stereoisomers include, but are not limited to,
compounds of formula (I) wherein R6 is a group having a stereogenic
center, such as a group --NH--C(O)--CH(CH.sub.3)--OCH.sub.3.
[3847] Each of said stereogenic centers may have the absolute
configuration R or the absolute configuration S (according to the
rules of Cahn, Ingold and Prelog).
[3848] The invention relates to the pure stereoisomers and to
mixtures of the stereoisomers independent of the ratio, including
the racemates. Accordingly, the invention relates to the pure
(cis)-isomers, the pure (trans)-isomers, and mixtures thereof, the
pure (R)-isomers, the pure (S)-isomers, and mixtures thereof.
[3849] Furthermore, the invention includes the pure
(trans,R)-isomers, (trans,S)-isomers, (cis,R)-isomers and
(cis,S)-isomers, and mixtures of two or more thereof in any ratio.
An example of said isomers is shown below:
##STR00007## ##STR00008##
[3850] Furthermore, the invention includes the pure (R,R)-isomers,
(R,S)-isomers, (S,R)-isomers and (S,S)-isomers, and mixtures of two
or more thereof in any ratio. An example of said isomers is shown
below:
##STR00009##
[3851] Furthermore, derivatives of the compounds according to the
invention, the salts thereof, the N-oxides of the compounds or the
salts thereof, the stereoisomers of the compounds, salts, N-oxides
of the compounds or N-oxides of the salts thereof which are
converted into compounds according to the invention, the salts
thereof, an N-oxide of the compound or the salt thereof, the
stereoisomers of the compounds, the salt, the N-oxide of the
compound or the N-oxide of the salt thereof in a biological system
(bioprecursors or pro-drugs) are covered by the invention. Said
biological system is e.g. a mammalian organism, particularly a
human subject. The bioprecursor is, for example, converted into the
compounds according to the invention, the salts thereof, an N-oxide
of the compound or the salt thereof, or a stereoisomers of the
compounds, the salt, the N-oxide of the compound or the N-oxide of
the salt thereof by metabolic processes.
[3852] The compounds according to the invention can be prepared as
follows.
##STR00010##
[3853] The compound of formula (I) can be obtained as shown in
reaction scheme 1 according to the procedures described in US
2005/0124623A1.
##STR00011##
[3854] As shown in reaction scheme 2, synthesis of a boronic acid
derivative of formula (2) may start from phenols of formula (11)
wherein R21, R22, R23 and R24 have the above defined meanings. The
phenols of formula (11) are commercially available or can be
prepared by methods known to a person skilled in the art. In a
first step R1, which has the above defined meaning, may be
introduced by alkylation. The alkylation is for example carried out
by suspending sodium hydride in an organic solvent, such as
dimethylethane (DME) or dimethylsulfoxide (DMSO) or a mixture
thereof, adding a solution of compound (II) in an organic solvent,
such as DME, at a temperature in the range of from 0 to 40.degree.
C., then adding a compound R1-halogen, preferably R1-Br or R1-I,
and reacting the mixture at a temperature of from 20 to 80.degree.
C. for 1 to 48 h to give a compound of formula (12). In a second
step, directed ortho-metalation followed by reaction with a boron
electrophile leads to the compounds of formula (2) wherein R1, R21,
R22, R23 and R24 have the above defined meanings, and Ra and Rb
represent 1-4C-alkyl or hydrogen, preferably Ra and Rb combine to
form a straight-chain or branched alkylene group having 2 to 8
carbon atoms, for example without limitation
--C(CH.sub.3).sub.2--C(CH.sub.3).sub.2--. In particular, a solution
of compound (12) in an organic solvent, such as tetrahydrofuran
(THF), can be reacted with n-butyl lithium (n-BuLi) in an organic
solvent, such as hexane, at a temperature of from -78 to 0.degree.
C. for 0.5 to 4 h. Subsequently, for example commercially available
2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane is added and
the reaction is performed at a temperature of from -78 to 0.degree.
C. for 0.5 to 3 h to yield a compound of formula (2).
##STR00012##
[3855] An alternative preparation of compounds of formula (2) is
shown in reaction scheme 3. The preparation may start from phenols
of formula (11), wherein R21, R22, R23 and R24 have the above
defined meanings and which are commercially available or can be
prepared by methods known to a person skilled in the art or as for
example described in Yamamoto, Y.; Hattori, K.; Ishii, J.-I.;
Nishiyama, H. Tetrahedron, 2006, 62, 4294. The phenols of formula
(11) are for example reacted with bromine or N-bromosuccinimide in
an organic solvent such as dichloromethane (DCM) at a temperature
of from -40 to 20.degree. C. for 0.5 to 4 h to give compounds of
formula (13). In a second step R1, which has the above defined
meaning, may be introduced by alkylation. The alkylation is for
example carried out by suspending sodium hydride in an organic
solvent, such as dimethylethane (DME) or dimethylsulfoxide (DMSO)
or a mixture thereof, adding a solution of compound (13) in an
organic solvent, such as DME, at a temperature in the range of from
0 to 40.degree. C., then adding a compound R1-halogen, preferably
R1-Br or R1-I, and reacting the mixture at a temperature of from 20
to 80.degree. C. for 1 to 48 h leading to compounds of formula
(14). In a third step, halogen-lithium exchange followed by
reaction with a boron electrophile yields the compounds of formula
(2), wherein R1, R21, R22, R23 and R24 have the above defined
meanings, and Ra and Rb represent 1-4C-alkyl or hydrogen,
preferably Ra and Rb combine to form a straight-chain or branched
alkylene group having 2 to 8 carbon atoms, for example without
limitation --C(CH.sub.3).sub.2--C(CH.sub.3).sub.2--. In particular,
a solution of compound (14) in an organic solvent, such as
tert-butylmethylether, can be reacted with n-BuLi (n-butyl lithium)
in an organic solvent, such as hexane, at a temperature of from -78
to 0.degree. C. for 0.5 to 3 h. Subsequently, for example
commercially available
2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane is added and
the reaction is performed at a temperature of from -78 to 0.degree.
C. for 0.5 to 3 h to yield a compound of formula (2).
##STR00013##
[3856] According to a further alternative preparation method shown
in reaction scheme 4, synthesis of boronic acid derivatives of
formula (2) may start from phenols of formula (11) wherein R21,
R22, R23 and R24 have the above defined meanings and which are
commercially available or can be prepared by methods known to a
person skilled in the art. In a first step R1, which has the above
defined meaning, is introduced by alkylation. The alkylation is for
example carried out by suspending sodium hydride in an organic
solvent, such as dimethylethane (DME) or dimethylsulfoxide (DMSO)
or a mixture thereof, adding a solution of compound (II) in an
organic solvent, such as DME, at a temperature in the range of from
0 to 40.degree. C., then adding a compound R1-halogen, preferably
R1-Br or R1-I, and reacting the mixture at a temperature of from 20
to 80.degree. C. for 1 to 48 h to give a compound of formula (12).
In a second step, compound (14) may be prepared for example from
compound (12) by reaction with N-bromosuccinimide in an organic
solvent, such as dimethylformamide, at a temperature of from 0 to
60.degree. C. for 0.5 to 5 h. In a third step, halogen-lithium
exchange followed by reaction with a boron electrophile yields the
compounds of formula (2), wherein R1, R21, R22, R23 and R24 have
the above defined meanings, and Ra and Rb represent 1-4C-alkyl or
hydrogen, preferably Ra and Rb combine to form a straight-chain or
branched alkylene group having 2 to 8 carbon atoms, for example
without limitation --C(CH.sub.3).sub.2--C(CH.sub.3).sub.2--. In
particular, a solution of compound (14) in an organic solvent, such
as tert-butylmethylether, can be reacted with n-BuLi (n-butyl
lithium) in an organic solvent, such as hexane, at a temperature of
from -78 to 0.degree. C. for 0.5 to 3 h. Subsequently, for example
commercially available
2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane is added and
the reaction is performed at a temperature of from -78 to 0.degree.
C. for 0.5 to 3 h to yield a compound of formula (2).
Alternatively, compounds of formula (2) may be synthesized from
compounds of formula (14) and an appropriate boron compound, such
as bis(pinacolato)diboron, in the presence of a Pd catalyst, such
as 1,1'-bis(diphenyl-phosphino)ferrocene palladium-(II)-chloride,
and a base, such as potassium acetate, in an organic solvent, such
as dioxane, at a temperature of from 20 to 100.degree. C. for 1 to
24 h. The Pd catalyzed preparation of boronic acid derivatives is,
for example, described in Murata et al, J Org Chem 2000, 65, 6458
and J Org Chem 1997, 52, 164.
##STR00014##
[3857] Reaction scheme 5 illustrates the synthesis of compounds of
formula (4) in which R1, R21, R22, R23 and R24 have the above
defined meanings. In a first step, compound (1) prepared according
to reaction scheme 1 can be reacted with a compound of formula (2)
prepared according to any of reaction scheme 2, 3 or 4, wherein R1,
R21, R22, R23, R24, Ra and Rb have the above defined meanings, to
obtain a compound of formula (3). In particular, the compound of
formula (I), a base, such as K.sub.2CO.sub.3, Cs.sub.2CO.sub.3 or
K.sub.3PO.sub.4, a solvent, such as dimethoxyethane, and a Pd
catalyst, such as PdCl.sub.2(PCy.sub.3).sub.2 (Cy=cyclohexyl), are
preferably heated at a temperature in the range of from 60 to
160.degree. C. for 5 to 10 min, more preferably under microwave
irradiation. After cooling to ambient temperature (e.g. 20 to
25.degree. C.), a compound of formula (2) can be added to the
reaction mixture which is then preferably heated to a temperature
in the range of from 60 to 160.degree. C. for 10 to 120 min, more
preferably under microwave irradiation. The compound of formula (3)
thus obtained can then be reacted with an alkali hydroxide, such as
LiOH, in a solvent, preferably a mixture of an organic solvent,
such as dioxane, and water, at a temperature in the range of from
20 to 100.degree. C. for 1 to 48 h to yield a compound of formula
(4).
##STR00015##
[3858] As shown in reaction scheme 6, starting from compounds of
formula (4) prepared according to above reaction scheme 5,
compounds of formula (I-1), wherein R1, R21, R22, R23, R24 and Y
have the above defined meanings and R3 is a 4- to 7-membered
saturated heterocyclic ring containing one nitrogen atom and
optionally one oxygen atom, said heterocyclic ring being
substituted by R4 with R4 being --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, with R41, R42
and R43 having the above defined meanings, can be prepared by
reaction with compounds of formula (5), wherein Y has the above
defined meaning and R3 is a 4- to 7-membered saturated heterocyclic
ring containing one nitrogen atom and optionally one oxygen atom,
said heterocyclic ring being substituted by R4 with R4 being
--C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, with R41, R42 and R43 having the above defined
meanings, under standard amide bond forming conditions. The
compounds of formula (5) are commercially available or can be
prepared by methods known to a person skilled in the art. An
exemplified method for preparing compounds of formula (5) is shown
in reaction scheme 15 below. In particular, a dehydrating agent,
such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
hydrochloride, a base, such as triethylamine, and a catalyst, such
as 1-hydroxybenzotriazole, can be added to a compound of formula
(4) which is preferably dissolved or suspended in an organic
solvent, e.g. dichloromethane. After stirring the mixture e.g. for
0.3 to 2 h, preferably at ambient temperature (e.g. 20 to
25.degree. C.), a compound of formula (5) can be added and the
reaction is preferably performed at ambient temperature (e.g. 20 to
25.degree. C.) for 1 to 48 h to yield the compound of formula
(I-1).
##STR00016##
[3859] As shown in reaction scheme 7, compounds of formula (I-2),
wherein R1, R21, R22, R23, R24 and Y have the above defined
meanings and R3 is a 3-6C-cycloalkyl group substituted by R6, with
R6 being --NH--C(O)--R7 and R7 being 1-4C-alkyl, which is
optionally substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, with R71, R72 and R73 having the above defined meanings,
can be synthesized by reaction of compounds of formula (4) prepared
according to above reaction scheme 5, with compounds of formula
(6), wherein Y has the above defined meaning and R3 is a
3-6C-cycloalkyl group substituted by R6, with R6 being
--NH--C(O)--R7 and R7 being 1-4C-alkyl, which is optionally
substituted by R71, 3-6C-cycloalkyl, which is optionally
substituted by R72, or 1-4C-alkoxy, which is optionally substituted
by R73, with R71, R72 and R73 having the above defined meanings.
The compounds of formula (6) are commercially available or can be
prepared by methods known to a person skilled in the art. In
particular, a dehydrating agent, such as
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, a
base, such as triethylamine, and a catalyst, such as
1-hydroxybenzotriazole, can be added to a compound of formula (4)
which is preferably dissolved or suspended in an organic solvent,
such as dichloromethane. After stirring the mixture e.g. for 0.3 to
2 h preferably at ambient temperature (e.g. 20 to 25.degree. C.), a
compound of formula (6) can be added and the reaction is preferably
performed at ambient temperature (e.g. 20 to 25.degree. C.) for 1
to 48 h to yield the compound of formula (I-2).
##STR00017##
[3860] Compounds of formula (I-3), wherein R1, R21, R22, R23, R24
and Y have the above defined meanings and R3 is a 4- to 7-membered
saturated heterocyclic ring containing one nitrogen atom and
optionally one oxygen atom, said heterocyclic ring being
substituted by R4 with R4 being --C(O)--O--C(CH.sub.3).sub.3,
prepared according to reaction scheme 6 can be converted into
compounds of formula (I-4), wherein R1, R21, R22, R23, R24 and Y
have the above defined meanings and R3 is a non-substituted 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, as shown in reaction scheme 8. In
particular, HCl preferably dissolved in an organic solvent, such as
dioxane, can be added to the compound of formula (I-3) which is
preferably dissolved in an organic solvent, such as an alcohol,
e.g. 2-propanol. The reaction mixture is then preferably heated at
40 to 80.degree. C. for 1 to 4 h to yield the hydrochloride of the
compound of formula (I-4). The compound of formula (I-4) can be
prepared from said hydrochloride as known to a person skilled in
the art, such as by treatment with a base, e.g. aqueous potassium
carbonate or aqueous ammonia.
##STR00018##
[3861] Compounds of formula (I-5), wherein R1, R21, R22, R23, R24
and Y have the above defined meanings and R3 is a 3-6C-cycloalkyl
group substituted by R6 with R6 being --NH--C(O)--R7 and R7 being
--O--C(CH.sub.3).sub.3, prepared according to reaction scheme 7 can
be converted into compounds of formula (I-6), wherein R1, R21, R22,
R23, R24 and Y have the above defined meanings and R3 is a
3-6C-cycloalkyl group substituted by R6 with R6 being --NH.sub.2 as
shown in reaction scheme 9. In particular, HCl preferably dissolved
in an organic solvent, such as dioxane, can be added to the
compound of formula (I-5) which is preferably dissolved in an
organic solvent, such as an alcohol, e.g. 2-propanol. The reaction
mixture is then preferably heated at 40 to 80.degree. C. for 1 to 4
h to yield the hydrochloride of the compound of formula (I-6). The
compound of formula (I-6) can be prepared from said hydrochloride
as known to a person skilled in the art, such as by treatment with
a base, e.g. aqueous potassium carbonate or aqueous ammonia.
##STR00019##
[3862] Alternatively, as shown in reaction scheme 10, compounds of
formula (I-1), wherein R1, R21, R22, R23, R24 and Y have the above
defined meanings and R3 is a 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom, with R4 being --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, and R41, R42 and
R43 are as defined above, may be prepared from compounds of formula
(I-4), wherein R1, R21, R22, R23, R24 and Y have the above defined
meanings and R3 is a non-substituted 4- to 7-membered saturated
heterocyclic ring containing one nitrogen atom and optionally one
oxygen atom prepared according to reaction scheme 8. In particular,
a compound R4 --Cl can be added to the compound of formula (I-4)
which is preferably dissolved in an organic solvent, such as
dichloromethane, in the presence of a base, such as
diazabicycloundecene (DBU). The compound of formula R4 --Cl is
commercially available or can be prepared by methods known to a
person skilled in the art. The addition is preferably carried out
at a temperature of from 0 to 20.degree. C. After complete
addition, the reaction is preferably continued at ambient
temperature (e.g. 20 to 25.degree. C.) for 1 to 24 h. In case R41,
R42 or R43 represent hydroxy, it is known to a person skilled in
the art that the hydroxy group is preferably to be protected by a
suitable protecting group, such as an acetate group or a silyl
protective group, e.g. a tert-butyl-dimethylsilyl group or a
tert-butyl-diphenylsilyl group. Said protective groups can be
removed by methods known to a person skilled in the art with or
without prior isolation of the protected intermediate (i.e. the
compound of formula (I-1) in its protected form).
##STR00020##
[3863] Alternatively, as shown in reaction scheme 11, compounds of
formula (I-2), wherein R1, R21, R22, R23, R24 and Y have the above
defined meanings and R3 is a 3-6C-cycloalkyl group substituted by
R6, with R6 being --NH--C(O)--R7, with R7 being 1-4C-alkyl, which
is optionally substituted by R71, 3-6C-cycloalkyl, which is
optionally substituted by R72, or 1-4C-alkoxy, which is optionally
substituted by R73, and R71, R72 and R73 are as defined above, may
be prepared from compounds of formula (I-6), wherein R1, R21, R22,
R23, R24 and Y have the above defined meanings and R3 is a
3-6C-cycloalkyl group substituted by R6 with R6 being NH.sub.2
prepared according to reaction scheme 9. In particular, a compound
R7-C(O)--Cl can be added to the compound of formula (I-6) which is
preferably dissolved in an organic solvent, such as
dichloromethane, in the presence of a base, such as
diazabicycloundecene (DBU). The compound of formula R7-C(O)--Cl is
commercially available or can be prepared by methods known to a
person skilled in the art. The addition is preferably carried out
at a temperature of from 0 to 20.degree. C. After complete
addition, the reaction is preferably continued at ambient
temperature (e.g. 20 to 25.degree. C.) for 1 to 24 h to yield the
compound of formula (I-2). In case R71, R72 or R73 represent
hydroxy, it is known to a person skilled in the art that the
hydroxy group is preferably to be protected by a suitable
protecting group, such as an acetate group or a silyl protective
group, e.g. a tert-butyl-dimethylsilyl group or
tert-butyl-diphenylsilyl group. Said protective groups can be
removed by methods known to a person skilled in the art with or
without prior isolation of the protected intermediate (i.e. the
compound of formula (I-2) in its protected form).
##STR00021##
[3864] As shown in reaction scheme 12, compounds of formula (I-7),
wherein R1, R21, R22, R23, R24 and Y have the above defined
meanings and R3 is a 4- to 7-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom, said
heterocyclic ring being substituted by R4, with R4 being --C(O)--H
can be prepared from compounds of formula (I-4), wherein R1, R21,
R22, R23, R24 and Y have the above defined meanings and R3 is a
non-substituted 4- to 7-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom
prepared according to reaction scheme 8. In particular, the
compound R4-O--C(O)--CH.sub.3, which can be prepared by methods
known to a person skilled in the art, can be added to the compound
of formula (I-4) which is preferably dissolved in an organic
solvent, such as dichloromethane, in the presence of a base, such
as diazabicycloundecene (DBU). The addition is preferably carried
out at a temperature of from 0 to 20.degree. C. After completion of
addition, the reaction is preferably continued at ambient
temperature (e.g. 20 to 25.degree. C.) for 1 to 24 h to yield the
compound of formula (I-7).
##STR00022##
[3865] As shown in reaction scheme 13, compounds of formula (I-8),
wherein R1, R21, R22, R23, R24 and Y have the above defined
meanings and R3 is a 3-6C-cycloalkyl group substituted by R6 with
R6 being --NH--C(O)--R7 with R7 being hydrogen can be prepared from
compounds of formula (I-6), wherein R1, R21, R22, R23, R24 and Y
have the above defined meanings and R3 is a 3-6C-cycloalkyl group
substituted by R6 with R6 being --NH.sub.2, obtained according to
reaction scheme 9. In particular, the compound
R7-C(O)--O--C(O)--CH.sub.3 with R7 being hydrogen, which can be
prepared by methods known to a person skilled in the art, can be
added to the compound of formula (I-6) which is preferably
dissolved in an organic solvent, such as dichloromethane, in the
presence of a base, such as diazabicycloundecene (DBU). The
addition is preferably carried out at a temperature of from 0 to
20.degree. C. After completion of addition, the reaction is
preferably continued at ambient temperature (e.g. 20 to 25.degree.
C.) for 1 to 24 h to yield a compound of formula (I-8).
##STR00023##
[3866] As shown in reaction scheme 14, compounds of formula (I-9),
wherein R1, R21, R22, R23, R24 and Y have the above defined
meanings and R3 is a 3-6C-cycloalkyl group substituted by R6, with
R6 being --C(O)--NR8R9, with R8 and R9 having the above defined
meanings, can be synthesized by reaction of compounds of formula
(4) prepared according to above reaction scheme 5, with compounds
of formula (7), wherein Y has the above defined meaning and R3 is a
3-6C-cycloalkyl group substituted by R6, with R6 being
--C(O)--NR8R9, with R8 and R9 having the above defined to meanings.
The compounds of formula (7) are commercially available or can be
prepared by methods known to a person skilled in the art. An
exemplified method for preparing compounds of formula (7) is shown
in reaction scheme 16 below. In particular, a dehydrating agent,
such as 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
hydrochloride, a base, such as triethylamine, and a catalyst, such
as 1-hydroxybenzotriazole, can be added to a compound of formula
(4) which is preferably dissolved or suspended in an organic
solvent, such as dichloromethane. After stirring the mixture e.g.
for 0.3 to 2 h preferably at ambient temperature (e.g. 20 to
25.degree. C.), a compound of formula (7) can be added and the
reaction is preferably performed at ambient temperature (e.g. 20 to
25.degree. C.) for 1 to 48 h to yield the compound of formula
(I-9).
##STR00024##
[3867] A compound of formula (5) with Y having the above defined
meaning and R3 being a 4- to 7-membered saturated heterocyclic ring
containing one nitrogen atom and optionally one oxygen atom
substituted by R4 with R4 being --C(O)-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R41,
--C(O)-3-6C-cycloalkyl, wherein the 3-6C-cycloalkyl group is
optionally substituted by R42, or --C(O)--O-1-4C-alkyl, wherein the
1-4C-alkyl group is optionally substituted by R43, with R41, R42
and R43 having the above defined meanings, can be prepared by
reacting a compound of formula NH.sub.2--Y--R3 with Y having the
above defined meaning and R3 being a non-substituted 4- to
7-membered saturated heterocyclic ring containing one nitrogen atom
and optionally one oxygen atom, in which compound the --NH.sub.2
group is protected by a suitable protecting group, such as a
tert-butoxycarbonyl group, with a compound of formula Cl--R4 with
R4 being --C(O)-1-4C-alkyl, wherein the 1-4C-alkyl group is
optionally substituted by R41, --C(O)-3-6C-cycloalkyl, wherein the
3-6C-cycloalkyl group is optionally substituted by R42, or
--C(O)--O-1-4C-alkyl, wherein the 1-4C-alkyl group is optionally
substituted by R43, with R41, R42 and R43 having the above defined
meanings, and subsequent removal of the protective group. In
particular, a compound of the formula Cl--R4 can be added to a
solution of a compound of formula NH.sub.2--Y--R3 in an organic
solvent, such as dichloromethane, containing a base, such as
Huenigs base at a temperature of from 0 to 25.degree. C. The
mixture is then stirred for 1 to 48 h at ambient temperature (e.g.
20 to 25.degree. C.). The protective group can be removed by
methods known to a person skilled in the art, such as by treatment
with hydrochloric acid in an organic solvent, such as dioxane or an
alcohol, e.g. iso-propanol. The hydrochloride of the compound of
formula (5) thus obtained can be converted into the compound of
formula (5) by methods known to a person skilled in the art, such
as treatment with a base, e.g. potassium carbonate or aqueous
ammonia. In case R41, R42 or R43 represent hydroxy, it is known to
a person skilled in the art to protect the hydroxy group by a
suitable protecting group, such as an acetate group or a silyl
protective group, e.g. a tert-butyl-dimethylsilyl group or
tert-butyl-diphenylsilyl group. Said protective group can be
removed by methods known to a person skilled in the art with or
without prior isolation of the protected intermediate (i.e. the
compound of formula (5) in its protected form).
##STR00025##
[3868] As shown in reaction scheme 16, a compound of formula (7)
with R3 being a 3-6C-cycloalkyl group substituted by R6 and R6
being --C(O)--NR8R9 can be prepared by reacting a compound of
formula NH.sub.2--R3-COOH, in which R3 is a 3-6C-cycloalkyl group
and wherein the --NH.sub.2 group is protected by a suitable
protecting group, such as a tert-butoxycarbonyl group, with a
compound of formula NHR8R9, in which R8 and R9 have the above
defined meanings, and subsequent removal of the protective group.
In particular, a dehydrating agent, such as
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI)
can be added to a mixture of a compound of formula
NH.sub.2--R3-COON, wherein the --NH.sub.2 group is protected by a
suitable protecting group, and a compound of formula NHR8R9 in an
organic solvent, such as dichloromethane. The reaction is
preferably performed at ambient temperature (e.g. 20 to 25.degree.
C.) for 1 to 48 hours. The protective group can be removed by
methods known to a person skilled in the art, such as by treatment
with hydrochloric acid in an organic solvent, such as dioxane or an
alcohol, e.g. iso-propanol. The hydrochloride of the compound of
formula (7) thus obtained can be converted into the compound of
formula (7) by methods known to a person skilled in the art, such
as by treatment with a base, e.g. potassium carbonate or aqueous
ammonia. In case R9 is substituted by R91 or R92 with R91 or R92
being hydroxy, it is known to a person skilled in the art to
protect the hydroxy group by a suitable protecting group, such as
an acetate group or a silyl protective group, e.g. a
tert-butyl-dimethylsilyl group or tert-butyl-diphenylsilyl group.
Said protective group can be removed by methods known to a person
skilled in the art with or without prior isolation of the protected
intermediate (i.e. the compound of formula (7) in its protected
form).
[3869] It is known to the person skilled in the art that, if there
are a number of reactive centers on a starting or intermediate
compound, it may be necessary to block one or more reactive centers
temporarily by protective groups in order to allow a reaction to
proceed specifically at the desired reaction center.
[3870] The compounds according to the invention are isolated and
purified in a manner known per se, e.g. by distilling off the
solvent in vacuo and recrystallizing the residue obtained from a
suitable solvent or subjecting them to one of the customary
purification methods, such as column chromatography on a suitable
support material.
[3871] Salts of the compounds of formula (I), the N-oxides thereof
and the stereoisomers of the compounds and the N-oxides thereof can
be obtained by dissolving the free compound in a suitable solvent
(for example a ketone such as acetone, methylethylketone or
methylisobutylketone, an ether such as diethyl ether,
tetrahydrofurane or dioxane, a chlorinated hydrocarbon such as
methylene chloride or chloroform, a low molecular weight aliphatic
alcohol such as methanol, ethanol or isopropanol, a low molecular
weight aliphatic ester such as ethyl acetate or isopropyl acetate,
or water) which contains the desired acid or base, or to which the
desired acid or base is then added. The acid or base can be
employed in salt preparation, depending on whether a mono- or
polybasic acid or base is concerned and depending on which salt is
desired, in an equimolar quantitative ratio or one differing
therefrom. The salts are obtained by filtering, reprecipitating,
precipitating with a non-solvent for the salt or by evaporating the
solvent. Salts obtained can be converted into the free compounds
which, in turn, can be converted into salts. In this manner,
pharmaceutically unacceptable salts, which can be obtained, for
example, as process products in the manufacturing on an industrial
scale, can be converted into pharmaceutically acceptable salts by
processes known to the person skilled in the art.
[3872] The compounds of formula (I), the salts thereof and the
stereoisomers of the compounds and the salts according to the
invention can be converted into their N-oxides, for example, by
reaction with peracids, such as m-chloroperbenzoic acid or
peracetic acid. The person skilled in the art is familiar with the
reaction conditions for carrying out the N-oxidation.
[3873] Pure diastereomers and pure enantiomers of the compounds of
formula (I) and the salts thereof, the N-oxides of the compounds
and the N-oxides of the salts can be obtained e.g. by asymmetric
synthesis, by using chiral starting compounds in synthesis and/or
by splitting up enantiomeric and diasteriomeric mixtures obtained
in synthesis. Preferably, the pure diastereomeric and pure
enantiomeric compounds of the invention are obtainable by using
chiral starting compounds in synthesis and/or by splitting up
enantiomeric and diasteriomeric mixtures obtained in synthesis.
[3874] Enantiomeric and diastereomeric mixtures can be split up
into the pure enantiomers and pure diastereomers by methods known
to a person skilled in the art. Preferably, diastereomeric mixtures
are separated by crystallization, in particular fractional
crystallization, or chromatography. Enantiomeric mixtures can be
separated e.g. by forming diastereomers with a chiral auxiliary
agent, resolving the diastereomers obtained and removing the chiral
auxiliary agent. As chiral auxiliary agents, for example, chiral
acids can be used to separate enantiomeric bases and chiral bases
can be used to separate enantiomeric acids via formation of
diastereomeric salts. Furthermore, diastereomeric derivatives such
as diastereomeric esters can be formed from enantiomeric mixtures
of alcohols or enantiomeric mixtures of acids, respectively, using
chiral acids or chiral alcohols, respectively, as chiral auxiliary
agents. Additionally, diastereomeric complexes or diastereomeric
clathrates may be used for separating enantiomeric mixtures.
Alternatively, enantiomeric mixtures can be split up using chiral
separating columns in chromatography. Another suitable method for
the isolation of enantiomers is the enzymatic separation.
[3875] All patents, patent applications, publications, test methods
and other materials cited herein are incorporated by reference in
their entireties.
[3876] The following examples illustrate the invention in greater
detail, without restricting it. Further compounds according to the
invention, of which the preparation is not explicitly described,
can be prepared in an analogous way.
[3877] The compounds, salts and stereoisomers which are mentioned
in the examples, and the salts of the compounds which are mentioned
in the examples, and the stereoisomers of the compounds mentioned
in the examples, the stereoisomers of the salts which are mentioned
in the examples and the stereoisomers of the salts of the compounds
which are mentioned in the examples represent preferred embodiments
of the invention.
[3878] The compounds which are mentioned in the examples, the salts
thereof, N-oxides of the compounds and the salts thereof and
stereoisomers of the compounds, salts, N-oxides of the compounds
and N-oxides of the salts thereof represent preferred embodiments
of the invention.
EXAMPLES
[3879] The following abbreviations are used: min: minutes, h:
hour(s), DCM: dichloromethane, DCE: dichloroethane, THF:
tetrahydrofuran, EA: ethyl acetate, sesamol:
3,4-methylenedioxyphenol, brine: saturated sodium chloride
solution, DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene, Huenigs base:
N-ethyl-diisopropylamine, mp.: melting point, bp: boiling point,
RT: room temperature (20 to 25.degree. C.), ambient temperature: 20
to 25.degree. C., TLC: thin layer chromatography, HPLC: high
performance liquid chromatography, GC-MS (EI): gas chromatography
coupled to mass spectrometry with electron impact ionization, MS
(ESI): mass spectrometry with electron spray ionization,
.sup.1H-NMR: .sup.1H nuclear magnetic resonance spectroscopy
(chemical shifts are reported as ppm against tetramethylsilane as
internal standard, coupling constants J are reported in Hz).
Example A1
4-Fluoro-3-methoxymethoxy-phenol
[3880] Under an atmosphere of argon a stirred solution of
4-bromo-1-fluoro-2-methoxymethoxy-benzene from example A25 (47.0 g;
0.200 mol) in dry tert-BuOMe (1000.0 mL) is cooled to -78.degree.
C. before tert-BuLi (1.7 M solution in pentane; 247.0 mL; 0.420
mol) is added via syringe within 30 min. After complete addition
stirring is continue at -78.degree. C. for one hour.
2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (91.6 mL;
0.440 mol) is slowly syringed into the reaction mixture. After
complete addition the mixture is stirred at -78.degree. C. for 30
min. Stirring is continued without external cooling. At 0.degree.
C. internal temperature the reaction mixture is quenched with 1 M
citric acid (400.0 mL). The mixture is vigorously stirred for 30
min. The organic layer is separated. The aqueous layer is extracted
with tert-BuOMe (2.times.100 mL). The combined organic layers are
washed with saturated Na--HCO.sub.3 (250 mL) and concentrated to
about 500 mL under reduced pressure.
[3881] To the well stirred solution of the crude product
H.sub.2O.sub.2 (30% aqueous solution; 51.5 mL; 0.500 mol) is slowly
added at 0.degree. C. and the reaction mixture is stirred at
ambient temperature over night. The aqueous layer is separated. The
organic layer is washed with water (2.times.100 mL), 1M aqueous
Na.sub.2SO.sub.3 solution (several small portions) till free of
peroxide and dried over MgSO.sub.4. After filtration the solvent is
removed under reduced pressure. The residual oil is chromatographed
on silica gel (cyclohexane:AcOEt/9:1) to give the title compound as
colorless oil. Yield: 29.8 g.
[3882] GC-MS (EI): m/z=172 (M.sup.+); 45 (100%).
[3883] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 9.35 (s, 1H, --OH);
6.99 (dd, J.sub.1=11.3, J.sub.2=8.9, 1H); 6.64 (dd, J.sub.1=7.1,
J.sub.2=2.9, 1H); 6.36 (ddd, J.sub.1=8.9, J.sub.2=3.4, J.sub.3=2.9,
1H); 5.15 (s, 2H); 3.40 (s, 3H).
[3884] The following compounds are obtained analogously to the
procedure described in the above example A1.
Example A2
3-(1,1-Difluoro-methoxy)-4-fluoro-phenol
[3885] Starting from
4-bromo-2-(1,1-difluoro-methoxy)-1-fluoro-benzene (example A26) the
title compound is obtained as colorless oil.
[3886] GC-MS (EI): m/z=178 (M.sup.+); 128 (100%).
[3887] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 9.72 (s, 1H, --OH);
7.18 (t, J=74.0, 1H); 7.17 (dd, J.sub.1=10.8, J.sub.2=8.9, 1H);
6.70 (dd, J.sub.1=6.8, J.sub.2=2.8, 1H); 6.63 (ddd, J.sub.1=8.9,
J.sub.2=3.7, J.sub.3=2.8).
Example A3
2-Bromo-5-fluoro-4-methoxy-phenol
[3888] 3-Fluoro-4-methoxy-phenol (21.32 g; 0.15 mol) prepared
according to literature [Freedman, J.; Stewart, K. T.; J.
Heterocycl. Chem. 1989, 26, 1547-1554] is dissolved in dry
dichloromethane (300 mL). The well stirred reaction mixture is
cooled to -15.degree. C. (ice/salt). A solution of bromine (23.97
g; 0.15 mol) in dry dichloromethane (75 mL) is slowly dropped into
the reaction mixture. After complete addition stirring is continued
for one hour. Water (150 mL) containing sodium sulfite (3.0 g) is
added to the reaction mixture. Stirring is continued at ambient
temperature for 30 min. The organic layer is separated, washed with
water (100 mL) and dried over MgSO.sub.4 in the presence of
decolorizing charcoal. After filtration the solvent is completely
removed under reduced pressure.
[3889] The residue is crystallized from
tert-butylmethylether/hexane to give the title compound as a
colorless solid. Yield: 30.74 g.
[3890] GC-MS (EI): m/z=222, 220 (M.sup.+); 207, 205
(M.sup.+-CH.sub.3, 100%); 179, 177.
[3891] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 10.06 (s, 1H, --OH);
7.28 (d, J=9.2, 1H); 6.81 (d, J=12.6, 1H); 3.76 (s, 3H).
[3892] The following compound is obtained analogously to the
procedure described in above example A3.
Example A4
2-Bromo-4-fluoro-5-methoxy-phenol
[3893] Starting from 4-fluoro-3-methoxy-phenol prepared according
to literature [Belanger, P. C.; Lau, C. K.; Williams, H. W. R.;
Dufresne, C.; Scheigetz, J. Can. J. Chem. 1988, 66, 1479-1482] the
title compound is obtained as colorless solid.
[3894] GC-MS (EI): m/z=222, 220 (M.sup.+, 100%); 207, 205
(M-CH.sub.3.sup.+); 179, 177.
[3895] .sup.1H-NMR (300 MHz, CDCl.sub.3): 7.16 (d, J=10.2, 1H);
6.67 (d, J=7.7, 1H); 5.29 (s, 1H, --OH); 3.85 (s, 3H)
Example A5
2-Bromo-5-(1,1-difluoro-methoxy)-4-fluoro-phenol
[3896] Starting from 3-(1,1-difluoro-methoxy)-4-fluoro-phenol
(example A2) the title compound is obtained as colorless oil.
[3897] GC-MS (EI): m/z=256, 258 (M.sup.+); 206, 208 (100%).
[3898] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 10.55 (s, 1H, --OH);
7.65 (d, J=10.0, 1H); 7.19 (t, J=73.0, 1H); 6.90 (d, J=7.3,
1H).
Example A6
1-(5-Bromo-4-cyclopropylmethoxy-2-methyl-phenyl)ethanone
[3899] A suspension of
1-(4-cyclopropylmethoxy-2-methyl-phenyl)-ethanone from example A24
(6.4 g, 31.3 mmol) and N-bromosuccinimide (6.20 g, 34.5 mmol) in
dry dimethylformamide (50 mL) is heated for 3 h at 50.degree. C.
After cooling to ambient temperature, water (200 mL) is added and
the mixture is extracted with ethyl acetate (3.times.60 mL). The
combined organic extracts are dried over sodium sulfate. The
solvent is removed under reduced pressure. The crude is purified by
column chromatography on silica gel using dichloromethane as eluent
to give the title compound as a off-white solid. Yield: 4.80 g.
[3900] MS (ESI): m/z=282 (MH.sup.+).
[3901] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 8.05 (s, 1H); 7.02 (m,
1H); 4.02 (d, J=6.0, 2H); 2.50 (s, 3H); 2.45 (s, 3H); 1.30 (m, 1H);
0.62 (m, 2H); 0.40 (m, 2H).
Example A7
2-Bromo-4-fluoro-5-methoxymethoxy-phenol
[3902] 4-Fluoro-3-methoxymethoxy-phenol from example A1 (6.89 g;
40.0 mmol) is dissolved in dry di-chloromethane (160.0 mL). The
stirred solution is cooled to -15.degree. C. N-bromosuccinimide
(7.12 g; 40.0 mmol) is added in small portions over one hour. After
complete addition the reaction mixture is stirred for another 30
min at -15.degree. C.
[3903] The reaction mixture is extracted with 2% aqueous sodium
sulfite solution (25.0 mL). The organic layer is separated. The
aqueous layer is extracted with dichloromethane (2.times.25.0 mL).
The combined organic layers are dried over MgSO.sub.4. The crude
material is chromatographed on silica gel
(dichloromethane:MeOH/99:01) to give the title compound as a
colorless solid. Yield: 8.33 g.
[3904] GC-MS (EI): m/z=250, 252 (M.sup.+); 45 (100%).
[3905] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 10.14 (s, 1H, --OH);
7.41 (d, J=10.8, 1H); 6.87 (d, J=7.8, 1H); 5.17 (s, 2H); 3.41 (s,
3H).
Example A8
5-Cyclopropylmethoxy-benzo[1,3]dioxole
[3906] Sodium hydride (60 wt % dispersion in mineral oil; 11.0 g;
275.0 mmol) is freed from oil by washing with hexane (2.times.50
mL) and suspended in dry DME (375 mL) and dry DMSO (37.5 mL). Under
an atmosphere of nitrogen a solution of commercially available
sesamol (3,4-methylenedioxy-phenol) (34.53 g; 250.0 mmol) in dry
DME (250 mL) is dropped into the well-stirred suspension at a rate
to keep the internal temperature below 40.degree. C. After complete
addition stirring is continued at ambient temperature for one
hour.
[3907] Neat commercially available bromomethyl-cyclopropane (37.13
g; 275.0 mmol) is added in one portion and the reaction mixture is
stirred at 80.degree. C. over night. Ice-cold water (125 mL) is
drop wise added and the reaction mixture is stirred for 30 min at
ambient temperature. After addition of brine (125 mL) the organic
layer is separated and concentrated in vacuo. The aqueous layer is
extracted with tert-butylmethylether (3.times.200 mL). All organic
phases are combined, washed with brine (200 mL), dried over
MgSO.sub.4 and filtered through a plug of neutral alumina
containing 5 wt % of water.
[3908] The product is completely eluted with several portions of
tert-butylmethylether. The solvent is removed under reduced
pressure. The remaining crude product is purified by short path
distillation at 3.times.10.sup.-3 mbar (117.degree. C.) to give the
title compound as colorless oil that solidifies at ambient
temperature. Yield: 47.28 g.
[3909] GC-MS (EI): m/z=192 (M.sup.+); 138 (M.sup.+-C.sub.4H.sub.6,
100%).
[3910] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 6.77 (d, J=8.5, 1H);
6.59 (d, J=2.5, 1H); 6.32 (dd, J.sub.1=8.5, J.sub.2=2.5, 1H); 5.93
(s, 2H); 3.71 (d, J=6.9, 2H); 1.15 (m, 1H); 0.53 (m, 2H); 0.27 (m,
2H).
[3911] The following compounds are obtained analogously to the
procedure described in above example A8.
Example A9
5-Cyclobutylmethoxy-benzo[1,3]dioxole
[3912] Starting from commercially available bromomethyl-cyclobutane
and sesamol the title compound is obtained as colorless solid.
[3913] GC-MS (EI): m/z=206 (M+); 138 (100%).
[3914] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.78 (d, J=8.4, 1H);
5.59 (d, J=2.5, 1H); 6.34 (dd, J.sub.1=8.4, J.sub.2=2.5, 1H); 5.94
(s, 2H); 3.85 (d, J=6.7, 2H); 2.66 (m, 1H); 2.05 (m, 2H); 1.93-1.76
(m, 4H).
Example A10
5-Ethoxy-benzo[1,3]dioxole
[3915] Starting from commercially available iodoethane and sesamol
the title compound is obtained as colorless oil.
[3916] GC-MS (EI): m/z=166 (M.sup.+); 138 (M.sup.+-C.sub.2H.sub.4);
137 (M.sup.+-C.sub.2H.sub.6, 100%).
[3917] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.78 (d, J=8.4, 1H);
6.59 (d, J=2.5, 1H); 6.33 (dd, J.sub.1=8.4, J.sub.2=2.5, 1H); 5.94
(s, 2H); 3.93 (qu, J=7.0, 2H); 1.28 (t, J=7.0, 3H).
Example A11
5-Propoxy-benzo[1,3]dioxole
[3918] Starting from commercially available iodopropane and sesamol
the title compound is obtained as colorless oil.
[3919] GC-MS (EI): m/z=180 (M.sup.+); 138 (M.sup.+-C.sub.3H.sub.6,
100%); 137 (M.sup.+-C.sub.3H.sub.7).
[3920] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.78 (d, J=8.4, 1H);
6.59 (d, J=2.5, 1H); 6.34 (dd, J.sub.1=8.4, J.sub.2=2.5, 1H); 5.94
(s, 2H); 3.83 (t, J=6.5, 2H); 1.68 (m, 2H); 0.95 (t, J=7.4,
3H).
Example A12
5-Butoxy-benzo[1,3]dioxole
[3921] Starting from commercially available bromobutane and sesamol
the title compound is obtained as colorless oil.
[3922] GC-MS (EI): m/z=194 (M.sup.+); 138 (M.sup.+-C.sub.4H.sub.8,
100%); 137 (M.sup.+-C.sub.4H.sub.9).
[3923] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.78 (d, J=8.4, 1H);
6.59 (d, J=2.5, 1H); 6.34 (dd, J.sub.1=8.4, J.sub.2=2.5, 1H); 5.94
(s, 2H); 3.87 (t, J=6.5, 2H); 1.65 (m, 2H); 1.41 (m, 2H); 0.92 (t,
J=7.4, 3H).
Example A13
5-(2-Methoxy-ethoxy)benzo[1,3]dioxole
[3924] Starting from commercially available
1-bromo-2-methoxy-ethane and sesamol the title compound is obtained
as colorless oil.
[3925] GC-MS (EI): m/z=196 (M.sup.+); 138 (M.sup.+-C.sub.3H.sub.6O,
100%); 59.
[3926] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.09 (d, J=8.5, 1H);
6.53 (d, J=2.5, 1H); 6.33 (dd, J.sub.1=8.5, J.sub.2=2.5, 1H); 5.90
(s, 2H); 4.04 (m, 2H); 3.71 (m, 2H); 3.44 (s, 3H).
Example A14
1-Bromo-2-cyclopropylmethoxy-4-methoxy-benzene
[3927] Starting from commercially available
2-bromo-5-methoxy-phenol and bromomethyl-cyclopropane the title
compound is obtained as colorless solid.
[3928] GC-MS (EI): m/z=258, 256 (M.sup.+).
[3929] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 7.41 (d, J=7.9, 1H);
6.48 (dd, J.sub.1=7.9, J.sub.2=2.2, 1H); 6.45 (d, J=2.2, 1H); 3.87
(d, J=5.6, 2H); 3.76 (s, 3H); 1.26 (m, 1H); 0.63 (m, 2H); 0.36 (m,
2H).
Example A15
1-Bromo-4-methoxy-2-(2-methoxy-ethoxy)-benzene
[3930] Starting from commercially available
2-bromo-5-methoxy-phenol and 1-bromo-2-methoxy-ethane the title
compound is obtained as colorless solid.
[3931] GC-MS (EI): m/z=260, 262 (M.sup.+); 202, 204
(M.sup.+-C.sub.3H.sub.6O, 100%).
[3932] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 7.40 (d, J=8.7, 1H);
6.51 (d, J=2.8, 1H); 6.41 (dd, J.sub.1=8.7, J.sub.2=2.8. 1H); 4.15
(t, J=4.8, 2H), 3.80 (t, J=4.8, 2H); 3.78 (s, 3H); 3.48 (s,
3H).
Example A16
1-Bromo-2-cyclopropylmethoxy-5-methoxy-benzene
[3933] Starting from commercially available
2-bromo-4-methoxy-phenol and bromomethyl-cyclopropane the title
compound is obtained as colorless oil.
[3934] GC-MS (EI): m/z=256, 258 (M.sup.+); 202, 204 (100%).
[3935] .sup.1H-NMR (200 MHz, CDCl.sub.3): 7.11 (d, J=2.8, 1H); 6.86
(d, J=8.9, 1H); 6.78 (dd, J.sub.1=8.9, J.sub.2=2.8, 1H); 3.82 (d,
J=6.8, 2H); 3.75 (s, 3H); 1.16 (m, 1H); 0.51 (m, 2H); 0.44 (m,
2H).
Example A17
1-Bromo-2-cyclopropylmethoxy-4-fluoro-benzene
[3936] Starting from commercially available 2-bromo-5-fluoro-phenol
and bromomethyl-cyclopropane the title compound is prepared as
colorless oil
[3937] GC-MS (EI): m/z=244, 246 (M.sup.+); 190, 192 (M.sup.+-C4H6);
55 (100%).
[3938] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.58 (dd, J.sub.1=8.7,
J.sub.2=6.4, 1H); 7.02 (dd, J.sub.1=11.2, J.sub.2=2.8, 1H); 6.75
(ddd, J.sub.1=J.sub.2=8.7, J.sub.3=2.8, 1H); 3.93 (d, J=6.8, 2H);
1.24 (m, 1H); 0.56 (m, 2H); 0.38 (m, 2H).
Example A18
1-Bromo-2-cyclopropylmethoxy-5-fluoro-benzene
[3939] Starting from commercially available 2-bromo-4-fluoro-phenol
and bromomethyl-cyclopropane the title compound is obtained as
colorless oil.
[3940] GC-MS (EI): m/z=244, 246 (M.sup.+); 190, 192;
(M.sup.+-C.sub.4H.sub.6); 55 (100%).
[3941] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 7.52 (dd, J.sub.1=8.2,
J.sub.2=3.1, 1H); 7.19 (ddd, J.sub.1=9.1, J.sub.2=8.2, J.sub.3=3.1,
1H); 7.10 (dd, J1=9.1, J2=5.0, 1H); 3.89 (d, J=6.8, 2H); 1.22 (m,
2H); 0.57 (m, 2H); 0.35 (m, 2H).
Example A19
1-Bromo-2-cyclopropylmethoxy-4-fluoro-5-methoxy-benzene
[3942] Starting from 2-bromo-5-fluoro-4-methoxy-phenol (example A3)
and bromomethyl-cyclopropane the title compound is obtained as
colorless solid.
[3943] GC-MS (EI): m/z=276, 274 (M.sup.+); 222, 220
(M.sup.+-C.sub.4H.sub.6, 100%); 206, 204.
[3944] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 7.38 (d, J=9.2, 1H);
7.13 (d, J=13.1, 1H); 3.85 (d, J=6.9, 2H); 3.80 (s, 3H); 1.20 (m,
1H); 0.57 (m, 2H); 0.33 (m, 2H).
Example A20
1-Bromo-2-cyclopropylmethoxy-5-fluoro-4-methoxy-benzene
[3945] Starting from commercially available
2-bromo-4-fluoro-5-methoxy-phenol (example A4) and
bromomethyl-cyclopropane the title compound is obtained as
colorless solid.
[3946] GC-MS (EI): m/z=276, 274 (M.sup.+); 222, 219
(M.sup.+-C.sub.4H.sub.6, 100%).
[3947] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 7.48 (d, J=10.8, 1H);
6.90 (d, J=7.9, 1H); 3.93 (d, J=6.8, 2H); 3.85 (s, 3H); 1.24 (m,
1H); 0.58 (m, 2H); 0.36 (m, 2H).
Example A21
1-Bromo-2-cyclopropylmethoxy-benzene
[3948] Starting from commercially available 2-bromo-phenol and
bromomethyl-cyclopropane the title compound is obtained as
colorless oil.
[3949] GC-MS (EI): m/z=226, 228 (M.sup.+); 172, 174
(M.sup.+-C.sub.4H.sub.6), 55 (100%).
[3950] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 7.56 (dd, J.sub.1=7.9,
J.sub.2=1.6, 1H); 7.31 (ddd, J.sub.1=8.3, J.sub.2=7.3, J.sub.3=1.6,
1H); 7.08 (dd, J.sub.1=8.3, J.sub.2=1.3, 1H); 6.87 (ddd,
J.sub.1=7.9, J.sub.2=7.3, J.sub.3=1.3, 1H); 3.91 (d, J=6.8, 2H);
1.24 (m, 1H); 0.58 (m, 2H); 0.35 (m, 2H).
Example A22
2-Bromo-1-cyclopropylmethoxy-4-methyl-benzene
[3951] Starting from commercially available 2-bromo-4-methyl-phenol
and bromomethyl-cyclopropane the title compound is obtained as
colorless oil.
[3952] GC-MS (EI): m/z=240, 242 (M.sup.+); 186, 188
(M.sup.+-C.sub.4H.sub.6); 107.
[3953] .sup.1H-NMR (300 MHz, CDCl3): 7.34 (d, J=2.1, 1H); 7.01 (dd,
J.sub.1=8.2, J.sub.2=2.1, 1H); 6.78 (d, J=8.2, 1H); 3.86 (d, J=6.8,
2H); 2.28 (s, 3H); 1.30 (m, 1H); 0.63 (m, 2H); 0.39 (m, 2H).
Example A23
1-(3-Bromo-4-cyclopropylmethoxy-phenyl)-ethanone
[3954] Starting from 1-(3-bromo-4-hydroxy-phenyl)-ethanone prepared
according to literature (Heravi et al, Tetrahedron Letters 2005,
46, 8959) and bromomethyl-cyclopropane the title compound is
obtained as colorless solid.
[3955] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 8.10 (d, J=2.0, 1H);
7.91 (dd, J.sub.1=8.0, J.sub.2=2.0, 1H); 7.18 (d, J=8.0, 1H); 4.03
(d, J=6.0, 2H); 2.50 (s, 3H); 1.30 (m, 1H); 0.62 (m, 2H); 0.40 (m,
2H).
Example A24
1-(4-Cyclopropylmethoxy-2-methyl-phenyl)-ethanone
[3956] Starting from commercially available
1-(4-hydroxy-2-methyl-phenyl)-ethanone and bromomethyl-cyclopropane
the title compound is obtained as pale yellow oil.
[3957] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.78 (d, J=2.0, 1H),
6.80 (m, 2H), 3.88 (d, J=6.0, 2H), 2.50 (s, 3H), 2.45 (s, 3H), 1.25
(m, 1H), 0.55 (m, 2H), 0.32 (m, 2H).
Example A25
4-Bromo-1-fluoro-2-methoxymethoxy-benzene
[3958] Starting from commercially available 5-bromo-2-fluoro-phenol
and 1-chloro-1-methoxy-methane prepared according to literature
(Stadlwieser, J. Synthesis 1985, 490) the title compound is
obtained as colorless oil.
[3959] GC-MS (EI): m/z=234, 236 (M.sup.+); 45 (100%).
[3960] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.45 (dd, J.sub.1=7.5,
J.sub.2=2.2, 1H); 7.28-7.17 (m, 2H); 5.28 (s, 2H); 3.41 (s,
3H).
Example A26
4-Bromo-2-(1,1-difluoro-methoxy)-1-fluoro-benzene
[3961] A pressure reactor is charged with commercially available
5-bromo-2-fluoro-phenol (95.50 g; 0.50 mol), 6N NaOH (500 mL; 3.0
mol) amd dioxane (500 mL). The reactor is pressurized with
1-chloro-1,1-difluoro-methane to 6.0 bar and heated to 80.degree.
C. for 72 hours.
[3962] The cooled reaction mixture is acidified to pH 2 by careful
addition of 6N HCl and extracted with tert.-BuOMe (1000
mL+2.times.200 mL). The combined organic layers are washed with
brine (300 mL) and dried over MgSO.sub.4. After filtration the
solvent is removed under reduced pressure. The product is separated
from remaining starting material by column chromatography on silica
gel (cyclohexane) to give the title compound as colorless oil.
Yield: 54.1 g.
[3963] GC-MS (EI): m/z=240, 242 (M.sup.+); 190, 192 (100%).
[3964] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.64 (dd, J.sub.1=7.1,
J.sub.2=2.4, 1H); 7.52 (ddd, J.sub.1=8.8, J.sub.2=4.2, J.sub.3=2.4,
1); 7.41 (dd, J.sub.1=10.4, J.sub.2=8.8, 1H); 7.3 (T, J=73.0,
1H).
Example A27
1-Bromo-2-cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-benzene
[3965] Starting from 2-bromo-4-fluoro-5-methoxymethoxy-phenol
(example A7) and bromomethyl-cyclopropane the title compound is
obtained as colorless oil.
[3966] GC-MS (EI): m/z=304, 306 (M.sup.+); 45 (100%).
[3967] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.54 (d, J=10.4, 1H);
6.99 (d, J=7.7, 1H); 5.26 (s, 2H); 3.88 (d, J=6.9, 2H); 3.41 (s,
3H); 1.22 (m, 1H); 0.57 (m, 2H); 0.34 (m, 2H).
Example A28
1-Bromo-2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-benzene
[3968] Starting from
2-bromo-5-(1,1-difluoro-methoxy)-4-fluoro-phenol (example A5) and
bromomethyl-cyclopropane the title compound is obtained as
colorless oil.
[3969] GC-MS (EI): m/z=310, 312 (M.sup.+); 256, 258; 206, 208; 177,
179; 55 (100%).
[3970] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.78 (d, J=6.9, 1H);
7.25 (t, J=74.0, 1H); 7.13 (d, J=7.3, 1H); 3.92 (d, J=6.9, 2H);
1.23 (m, 1H); 0.58 (m, 2H); 0.35 (m, 2H).
Example A29
5-Cyclopropylmethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benz-
o[1,3]dioxole
[3971] The reaction is performed in flame-dried glassware under an
atmosphere of argon.
[3972] A stirred solution of 5-cyclopropylmethoxy-benzo[1,3]dioxole
from example A8 (38.44 g; 200.0 mmol) in dry THF (500 mL) is cooled
to -40.degree. C. before n-butyl lithium (138.0 mL; 1.6 M solution
in hexane; 220 mmol) is slowly added via syringe. After complete
addition, stirring is continued at -40.degree. C. for two hours. At
-78.degree. C. neat
2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (40.95 g;
220.0 mmol) is added via syringe and stirring is continued at
-78.degree. C. for two hours.
[3973] At -15.degree. C. the reaction mixture is quenched with
saturated NH.sub.4Cl-solution (200 mL) and stirred at ambient
temperature for 30 min. The organic layer is separated and
concentrated under reduced pressure. The aqueous layer is extracted
with tert-butylmethylether (3.times.200 mL). All organic phases are
combined, washed with saturated NaCl-solution (200 mL), dried over
MgSO.sub.4 and filtered through a plug of neutral alumina
containing 5 wt % of water. The product is completely eluted with
several small portions of tert-butylmethylether.
[3974] The solvent is removed under reduced pressure. The crude is
treated with ice-cold methanol (50 mL) to deliver the title
compound as colorless solid. Yield 54.32 g.
[3975] GC-MS (EI): m/z=318 (M.sup.+); 264 (M.sup.+-C.sub.4H.sub.6);
207; 164 (100%).
[3976] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 6.78 (d, J=8.4, 1H);
6.29 (d, J=8.4; 1H); 5.92 (s, 2H); 3.71 (d, J=6.3, 2H); 1.29 (s,
12H); 1.14 (m, 1H); 0.50 (m, 2H); 0.34 (m, 2H).
[3977] The following compounds are obtained analogously to the
procedure described in above example A29.
Example A30
5-Cyclobutylmethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo-
[1,3]dioxole
[3978] Starting from 5-cyclobutylmethoxy-benzo[1,3]dioxole (example
A9) the title compound is prepared as colorless solid.
[3979] GC-MS (EI): m/z=332 (M.sup.+); 164 (100%);
[3980] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 6.81 (d, J=8.4, 1H);
6.29 (d, J=8.4; 1H); 5.92 (s, 2H); 3.76 (d, J=6.0, 2H); 2.64 (m,
1H); 2.07-1.76 (m, 6H); 1.27 (s, 12H).
Example A31
5-Ethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxol-
e
[3981] Starting from 5-ethoxy-benzo[1,3]dioxole (example A10) the
title compound is prepared as color-less solid.
[3982] GC-MS (EI): m/z=292 (M.sup.+, 100%); 207; 164.
[3983] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.80 (d, J=8.4, 1H);
6.30 (d, J=8.4; 1H); 5.92 (s, 2H); 3.86 (qu, J=7.0, 2H); 1.27 (s,
12H); 1.25 (t, J=7.0, 3H).
Example A32
5-Propoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxo-
le
[3984] Starting from 5-propoxy-benzo[1,3]dioxole (example A11) the
title compound is prepared as color-less solid.
[3985] GC-MS (EI): m/z=306 (M.sup.+); 207 (100%); 164.
[3986] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.80 (d, J=8.4, 1H);
6.28 (d, J=8.4; 1H); 5.92 (s, 2H); 3.77 (t, J=6.2, 2H); 1.66 (m,
2H); 1.27 (s, 12H); 0.98 (t, J=7.4, 3H).
Example A33
5-Butoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxol-
e
[3987] Starting from 5-butoxy-benzo[1,3]dioxole (example A12) the
title compound is prepared as color-less solid.
[3988] GC-MS (EI): m/z=320 (M.sup.+); 207 (100%); 164.
[3989] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 6.80 (d, J=8.5, 1H);
6.29 (d, J=8.5; 1H); 5.92 (s, 2H); 3.81 (t, J=6.1, 2H); 1.62 (m,
2H); 1.46 (m, 2H); 1.26 (s, 12H); 0.91 (t, J=7.3, 3H).
Example A34
5-(2-Methoxy-ethoxy)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benz-
o[1,3]dioxole
[3990] Starting from 5-(2-methoxy-ethoxy)-benzo[1,3]dioxole
(example A13) the title compound is pre-pared as colorless
solid.
[3991] GC-MS (EI): m/z=322 (M.sup.+); 207 (100%); 164.
[3992] .sup.1H-NMR (200 MHz, CDCl.sub.3): 6.81 (d, J=8.5, 1H); 6.31
(d, J=8.5, 1H); 5.93 (s, 2H); 3.93 (m, 2H); 3.59 (m, 2H); 3.30 (s,
3H); 1.27 (s, 12H).
Example A35
2-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,-
3,2]dioxaborolane
[3993] The reaction is performed in flame-dried glassware under an
atmosphere of argon.
[3994] A stirred solution of
1-bromo-2-cyclopropylmethoxy-4-fluoro-5-methoxy-benzene from
example A19 (27.51 g; 0.10 mol) in dry tert-butylmethylether (500
mL) is cooled to -20.degree. C. before addition of n-butyl lithium
(1.6 M in hexane; 68.8 mL; 0.11 mol) via syringe. After complete
addition stirring is continued for one hour. Neat
2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane is added via
syringe into the reaction mixture at -40.degree. C. After 30 min
the reaction is quenched with 1M citric acid (200 mL) at 0.degree.
C. and stirred for one hour at ambient temperature. The organic
layer is separated. The aqueous layer is extracted with
tert-butylmethylether (100 mL). The combined organic layers are
washed with brine (200 mL) dried over MgSO.sub.4 and filtered
through a plug of neutral alumina containing 5 wt % of water. The
product is completely eluted with several small portions of
tert-butylmethylether. The solvent is removed under reduced
pressure. The crude is purified by short path distillation at
3.times.10.sup.-3 mbar (160.degree. C.) to give the title compound
as a colorless oil that solidifies at ambient temperature. Yield:
22.65 g.
[3995] GC-MS (EI): m/z=322 (M.sup.+, 100%); 211, 168. Purity:
>99.8%.
[3996] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.14 (d, J=10.5, 1H);
6.91 (d, J=13.6, 1H); 3.81 (d, J=6.0, 2H); 3.77 (s, 3H); 1.28 (s,
12H); 1.16 (m, 1H); 0.48 (m, 2H); 0.38 (m, 2H).
[3997] The following compounds are obtained analogously to the
procedure described in above example A35.
Example A36
2-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxa-
borolane
[3998] Starting from 1-bromo-2-cyclopropylmethoxy-4-methoxy-benzene
(example A14) the title compound is prepared as colorless solid
after crystallization from hexane.
[3999] GC-MS (EI): m/z=304 (M.sup.+); 276; 250; 193; 164 (100%);
150.
[4000] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 7.41 (d, J=7.9, 1H);
6.48 (dd, J.sub.1=7.9, J.sub.2=2.2, 1H); 6.45 (d, J=2.2, 1H); 3.87
(d, J=5.6, 2H); 3.75 (s, 3H); 1.25 (s, 12H); 1.16 (m, 1H); 0.49 (m,
2H); 0.44 (m, 2H).
Example A37
2-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxa-
borolane
[4001] Starting from 1-bromo-2-cyclopropylmethoxy-5-methoxy-benzene
(example A16) the title compound is obtained as colorless oil after
short path distillation at 3.times.10.sup.-3 mbar (160.degree.
C.).
[4002] GC-MS (EI): m/z=304 (M.sup.+); 276; 250; 193 (100%);
150.
[4003] .sup.1H-NMR (200 MHz, CDCl.sub.3): 7.15 (d, J=3.1, 1H); 6.90
(dd, J.sub.1=9.0, J.sub.2=3.1, 1H); 6.81 (d, J=9.0, 1H); 3.80 (d,
J=6.3, 2H); 3.78 (s, 3H); 1.35 (s, 12H); 1.17 (m, 1H); 0.55 (m,
2H); 0.38 (m, 2H).
Example A38
2-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxab-
orolane
[4004] Starting from 1-bromo-2-cyclopropylmethoxy-4-fluoro-benzene
(example A17) the title compound is obtained as colorless solid
after short path distillation at 3.times.10.sup.-3 mbar
(130.degree. C.).
[4005] GC-MS (EI): m/z=292 (M.sup.+); 181, 55 (100%).
[4006] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.48 (dd, J1=J2=8.0,
1H); 6.80 (dd, J1=12.0, J2=2.2, 1H); 6.71 (ddd, J1=8.4, J2=8.0,
J3=2.2, 1H); 3.89 (d, J=5.8, 2H); 1.27 (s, 12H); 1.17 (m, 1H); 0.51
(m, 2H); 0.46 (m, 2H).
Example A39
2-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxab-
orolane
[4007] Starting from 1-bromo-2-cyclopropylmethoxy-5-fluoro-benzene
(example A18) the title compound is obtained as colorless solid
after short path distillation at 3.times.10.sup.-3 mbar
(100.degree. C.).
[4008] GC-MS (EI): m/z=292 (M+); 181 (100%); 55.
[4009] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.22-7.13 (m, 2H); 6.95
(dd, J1=8.9, J2=4.2, 1H); 3.85 (d, J=6.4, 2H); 1.28 (s, 12H); 1.17
(m, 1H); 0.52 (m, 2H); 0.46 (m, 2H).
Example A40
2-(2-Cyclopropylmethoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane
[4010] Starting from 1-bromo-2-cyclopropylmethoxy-benzene (example
A21) the title compound is obtained as colorless viscous oil.
[4011] GC-MS (EI): m/z=274 (M+); 163; 120; 83; 55 (100%).
[4012] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.45 (dd, J.sub.1=7.4,
J.sub.2=1.7, 1H); 7.37 (ddd, J.sub.1=7.8, J.sub.2=6.9, J.sub.3=1.7,
1H); 6.91 (d, J=7.8, 1H); 6.89 (d, J=6.9, 1H); 3.86 (d, J=5.8, 2H);
1.28 (s, 12H); 1.20 (m, 1H); 0.50 (m, 2H); 0.44 (m, 2H).
Example A41
2-(2-Cyclopropylmethoxy-5-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxab-
orolane Starting from 1-bromo-2-cyclopropylmethoxy-5-methyl-benzene
(example A22) the title compound is obtained as colorless
solid.
[4013] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 7.26 (d, J=2.1, 1H);
7.16 (dd, J.sub.1=8.3, J.sub.2=2.1, 1H); 6.81 (d, J=8.3, 1H); 3.81
(d, J=5.9, 2H); 2.21 (s, 3H); 1.27 (s, 12H); 1.15 (m, 1H); 0.47 (m,
2H); 0.40 (m, 2H).
Example A42
2-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,-
3,2]dioxaborolane
[4014] Starting from
1-bromo-2-cyclopropylmethoxy-5-fluoro-4-methoxy-benzene (example
A20) the title compound is obtained as colorless solid after
crystallization from methanol.
[4015] GC-MS (EI): m/z=322 (M.sup.+); 211; 182; 168 (100%); 55.
[4016] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.15 (d, J=11.7, 1H);
6.73 (d, J=7.0, 1H); 3.88 (d, J=6.0, 2H); 3.85 (s, 3H); 1.26 (s,
12H); 1.16 (m, 1H); 0.50 (m, 2H); 0.30 (m, 2H).
Example A43
2-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxa-
borolane
[4017] Starting from 1-bromo-4-methoxy-2-(2-methoxy-ethoxy)-benzene
(example A15) the title compound is obtained as colorless solid
after crystallization from methanol.
[4018] GC-MS (EI): m/z=308 (M+); 250 (M+-C.sub.3H.sub.6O); 164
(100%).
[4019] .sup.1H-NMR (200 MHz, CDCl.sub.3): 7.61 (d, J=8.2, 1H); 6.49
(dd, J.sub.1=8.2, J.sub.2=2.2, 1H); 6.41 (d, J=2.2 1H); 4.10 (t,
J=5.4, 2H); 3.80 (s, 3H); 3.78 (t, J=5.4, 2H); 3.50 (s, 3H); 1.32
(s, 12H).
Example A44
2-(2-Cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-4,4,5,5-tetramet-
hyl-[1,3,2]dioxaborolane
[4020] Starting from
1-bromo-2-cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-benzene
(example A27) the title compound is obtained as colorless oil that
solidified on standing at ambient temperature after short path
distillation at 3.times.10.sup.-3 mbar (150.degree. C.).
[4021] GC-MS (EI): m/z=352 (M.sup.+); 45 (100%).
[4022] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.19 (d, J=11.3, 1H);
6.82 (d, J=6.8, 1H); 5.28 (s, 2H); 3.83 (d, J=6.0, 2H); 3.41 (s,
3H); 1.26 (s, 12H); 1.16 (m, 1H); 0.49 (m, 2H); 0.40 (m, 2H).
Example A45
2-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-4,4,5,5--
tetramethyl-[1,3,2]-dioxabolane
[4023] Starting from
1-bromo-2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-benzene
(example A28) the title compound is obtained as colorless oil after
short path distillation at 2.times.10.sup.-3 mbar (130.degree.
C.)
[4024] GC-MS (EI): 358 (M+); 330, 247, 204, 154, 83, 55 (100%).
[4025] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.41 (d, J=10.6, 1h);
6.69 (d, J=6.0, 1H); 6.55 (t, J=74.0, 1H); 3.83 (d, J=6.0, 2H);
1.34 (s, 12H); 1.23 (m, 1H); 0.57 (m, 2H); 0.42 (m, 2H).
Example A46
1-[4-Cyclopropylmethoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-p-
henyl]-ethanone
[4026] A suspension of
1-(3-Bromo-4-cyclopropylmethoxy-phenyl)-ethanone from example A23
(3.00 g, 11.1 mmol), potassium acetate (3.30 g, 33.3 mmol),
bis(pinacolato)diboron (5.70 g, 22.2 mmol) and
1,1'-bis(diphenyl-phosphino)ferrocene palladium-Op-chloride (0.90
g, 1.1 mmol) in 1,4-dioxane (50 mL) is heated under a nitrogen
atmosphere for 4 h at 100.degree. C. After cooling to ambient
temperature the solvent is evaporated. The mixture is purified by
column chromatography on silica gel (n-hexane/ethyl acetate (65:35
v/v) to give the title compound as a off white solid.
[4027] Yield: 3.13 g.
[4028] MS (ESI): m/z=317 (MH.sup.+, 100%).
[4029] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) 8.02 (m, 2H); 7.00 (m,
1H); 3.97 (d, J=6.0, 2H); 2.50 (s, 3H); 1.30 (s, 12H); 1.23 (m,
1H); 0.50 (m, 4H).
[4030] The following compound is obtained analogously to the
procedure described in above example A46.
Example A47
1-[4-Cyclopropylmethoxy-2-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborola-
n-2-yl)-phenyl]-ethanone
[4031] Starting from
1-(5-bromo-4-cyclopropylmethoxy-2-methyl-phenyl)-ethanone (example
A6) the title compound is obtained as off-white solid after column
chromatography on silica gel.
[4032] MS (ESI): m/z=331 (MH.sup.+, 100%).
[4033] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 7.95 (s, 1H); 6.83 (s,
1H); 3.98 (d, J=6.0, 2H); 2.50 (m, 6H); 1.35 (m, 1H); 1.30 (s,
12H); 0.60-0.30 (m, 4H).
Example A48
4-(5-Cyclopropylmethoxy-1,3
benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid
ethyl ester
[4034] A 25 ml pressure vial is charged with
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
(0.90 g; 4.0 mmol) prepared according to the procedure described in
US 2005/124623A1, 2M aqueous Cs.sub.2CO.sub.3 solution (6.0 mL),
dimethoxyethane (10.0 mL) and PdCl.sub.2(PCy.sub.3).sub.2 (236 mg,
0.32 mmol) (Cy=cyclohexyl). The mixture is heated to 150.degree. C.
for 5 min under microwave irradiation. After cooling to ambient
temperature,
5-cyclopropylmethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-ben-
zo[1,3]dioxole from example A29 (1.91 g; 5.0 mmol) is added to the
reaction vial and the mixture is heated to 150.degree. C. for 30
min under microwave irradiation.
[4035] After cooling to ambient temperature, water (10.0 mL) is
added. The precipitated crude product is collected by suction
filtration and washed with several small portions (10 to 25 mL) of
DME/water (1:2 v/v). Crude products from ten reactions are combined
and dissolved in hot DME. The hot solution is filtered through a
short column of neutral alumina containing 5 wt % of water. The
column is washed with several portions of hot DME. The combined
filtrates are evaporated to dryness. The crude is crystallized from
DME/toluene to give the title compound as colorless solid. Yield
11.58 g
[4036] MS (ESI): m/z=404 (MNa.sup.+); 382 (MH.sup.+, 100%).
[4037] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.36 (s, 1H, --NH);
9.01 (s, 1H); 8.39 (s, 1H); 7.00 (d, J=8.6, 1H); 6.56 (d, J=8.6,
1H); 5.99 (s, 2H); 4.31 (qu, J=7.1, 2H); 3.75 (d, J=6.7, 2H); 1.33
(t, J=7.1, 3H); 0.87 (m, 1H); 0.29 (m, 2H); 0.08 (m, 2H).
[4038] The following compounds are obtained analogously to the
procedure described in above example A48.
Example A49
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid ethyl ester
[4039] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
5-cyclobutylmethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benz-
o[1,3]dioxole (example A30) the title compound is obtained as
colorless solid.
[4040] MS (ESI): m/z=396 (MH.sup.+, 100%); 382
(MH.sup.+--CH.sub.2).
[4041] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.42 (br.s, 1H, --NH);
9.00 (s, 1H); 8.37 (d, J=3.0, 1H); 7.01 (d, J=8.6, 1H); 6.59 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.31 (qu, J=7.1, 2H); 3.84 (d, J=6.1,
2H); 2.36 (m, 1H); 1.65 (m, 3H); 1.50 (m, 3H); 1.33 (t, J=7.1,
3H).
Example A50
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid ethyl ester
[4042] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]diox-
aborolane (example A36) the title compound is obtained as colorless
solid.
[4043] MS (ESI): m/z=390 (MNa.sup.+); 368 (MH.sup.+, 100%); 354
(MH.sup.+--CH.sub.2).
[4044] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
8.98 (s, 1H); 8.32 (s, 1H); 7.59 (d, J=8.2, 1H); 6.72 (dd,
J.sub.1=8.2, J.sub.2=2.3, 1H); 6.69 (d, J=2.3, 1H); 4.31 (qu,
J=7.1, 2H); 3.91 (d, J=6.9, 2H); 3.86 (s, 3H); 1.33 (t, J=7.1, 3H);
0.96 (m, 1H); 0.35 (m, 2H); 0.23 (m, 2H).
Example A51
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid ethyl ester
[4045] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]diox-
aborolane (example A37) the title compound is obtained as colorless
solid.
[4046] MS (ESI): m/z=390 (MNa.sup.+); 368 (MH.sup.+, 100%); 354
(MH.sup.+--CH.sub.2).
[4047] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.10 (br.s, 1H, --NH);
9.04 (s, 1H); 8.36 (d, J=3.2, 1H); 7.19 (t, J=1.7, 1H); 7.11 (t,
J=1.7, 2H); 6.69 (d, J=2.3, 1H); 4.31 (qu, J=7.0, 2H); 3.81 (d,
J=6.8, 2H); 3.77 (s, 3H); 1.34 (t, J=7.0, 3H); 0.91 (m, 1H); 0.32
(m, 2H); 0.15 (m, 2H).
Example A52
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid ethyl ester
[4048] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-4-fluoro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxa-
borolane (example A38) the title compound is obtained as colorless
solid.
[4049] MS (ESI): m/z=378 (MNa.sup.+); 356 (MH.sup.+, 100%).
[4050] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.18 (br.s, 1H, --NH);
9.02 (s, 1H); 8.39 (s, 1H); 7.65 (dd, J.sub.1=8.4, J.sub.2=2.3,
1H); 7.08 (dd, J.sub.1=11.5, J.sub.2=2.3, 1H); 6.96 (ddd,
J.sub.1=J.sub.2=8.4, J.sub.3=2.3); 4.31 (qu, J=7.1, 2H); 3.91 (d,
J=7.0, 2H); 1.33 (t, J=7.1, 3H); 0.95 (m, 1H); 0.35 (m, 2H); 0.21
(m, 2H).
Example A53
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid ethyl ester
[4051] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-5-fluoro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxa-
borolane (example A39) the title compound is obtained as colorless
solid.
[4052] MS (ESI): m/z=378 (MNa.sup.+); 356 (MH.sup.+, 100%); 342
(MH.sup.+--CH.sub.2).
[4053] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.20 (br.s, 1H, --NH);
9.04 (s, 1H); 8.41 (s, 1H); 7.46-7.32 (m, 2H); 7.18 (dd,
J.sub.1=8.9, J.sub.2=4.4, 1H); 4.32 (qu, J=7.1, 2H); 3.87 (d,
J=6.9, 2H); 1.34 (t, J=7.1, 3H); 0.93 (m, 1H); 0.33 (m, 2H); 0.17
(m, 2H).
Example A54
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid ethyl ester
[4054] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane
(example A40) the title compound is obtained as colorless
solid.
[4055] MS (ESI): m/z=360 (MNa.sup.+); 338 (MH.sup.+); 324
(MH.sup.+--CH.sub.2, 100%).
[4056] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.17 (br.s, 1H, --NH);
9.04 (s, 1H); 8.38 (d, J=3.4, 1H); 7.62 (dd, =7.5 J.sub.2=1.2, 1H);
7.53 (ddd, J.sub.1=8.6, J.sub.2=7.5, J.sub.3=1.2, 1H); 7.17 (d,
J=8.6, 1H); 7.12 (d, J=7.5, 1H); 4.32 (qu, J=7.1, 2H); 3.90 (d,
J=6.9, 2H); 1.32 (t, J=7.1, 3H); 0.95 (m, 1H); 0.34 (m, 2H); 0.22
(m, 2H).
Example A55
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ethyl ester
[4057] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-4,4,5,5-tetramethyl-[1-
,3,2]dioxaborolane (example A35) the title compound is obtained as
colorless solid.
[4058] MS (ESI): m/z=389 (MH.sup.+, 100%)
[4059] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.11 (br.s, 1H, --NH);
9.03 (s, 1H); 8.38 (d, J=3.2, 1H, --NH); 7.39 (d, J=9.8, 1H); 7.18
(d, J=13.4, 1H); 4.31 (qu, J=7.1, 2H); 3.84 (s, 3H & d, J=5.1,
2H); 1.34 (t, J=7.1, 3H); 0.92 (m, 1H); 0.33 (m, 2H); 0.15 (m,
2H).
Example A56
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ethyl ester
[4060] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-4,4,5,5-tetramethyl-[1-
,3,2]dioxaborolane (example A42) the title compound is obtained as
pale yellow solid.
[4061] MS (ESI): m/z=408 (MNa.sup.+); 386 (MH.sup.+, 100%).
[4062] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.06 (br.s, 1H, --NH);
9.00 (s, 1H); 8.37 (d, J=2.7, 1H); 7.48 (d, J=11.9, 1H); 6.92 (d,
J=7.3, 1H); 4.32 (qu, J=7.1, sH); 3.97 (s, 3H); 3.94 (d, J=6.9,
2H); 1.34 (t, J=7.1, 3H); 0.96 (m, 1H); 0.37 (m, 2H), 0.21 (m,
2H).
Example A57
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid ethyl ester
[4063] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
1-[4-cyclopropylmethoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)--
phenyl]-ethanone (example A46) the title compound is obtained as
colorless solid.
[4064] MS (ESI): m/z=386 (MH.sup.+, 100%).
[4065] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.30 (s, 1H, --NH);
9.08 (s, 1H), 8.42 (d, J=3.5, 1H); 8.20 (d, J=1.5 Hz, 1H); 8.12
(dd, J.sub.1=9.0, J.sub.2=1.5, 1H); 7.25 (d, J=9.0, 1H); 4.34 (q,
J=7.0, 2H); 4.05 (d, J=7.0, 2H); 2.60 (s, 3H); 1.33 (t, J=7.0, 3H);
1.00 (m, 1H); 0.35 (m, 2H); 0.24 (m, 2H).
Example A58
4-(5-Acetyl-4-methyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carboxylic acid ethyl ester
[4066] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
1-[4-cyclopropylmethoxy-2-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborol-
an-2-yl)-phenyl]-ethanone (example A47) the title compound is
obtained as colorless solid.
[4067] MS (ESI): m/z=394 (MH.sup.+, 100%).
[4068] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.20 (s, 1H, --NH);
9.05 (s, 1H); 8.40 (s, 1H), 8.12 (s, 1H); 7.10 (s, 1H); 4.34 (q,
J=7.0, 2H); 3.95 (d, J=7.0, 2H); 2.60 (s, 3H); 2.55 (s, 3H); 1.33
(t, J=7.0, 3H), 0.95 (m, 1H); 0.38 (m, 2H); 0.24 (m, 2H).
Example A59
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid ethyl ester
[4069] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-(2-cyclopropylmethoxy-5-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxa-
borolane (example A41) the title compound is obtained as colorless
solid.
[4070] MS (ESI): m/z=352 (MNH.sup.+, 100%); 338
(MH.sup.+--CH.sub.2).
[4071] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.09 (br.s, 1H, --NH);
9.02 (s, 1H); 8.35 (s, 1H); 7.43 (s, 1H); 7.33 (d, J=8.5, 1H); 7.05
(d, J=8.5, 1H); 4.32 (qu, J=7.1, 2H); 3.86 (d, J=6.9, 2H); 2.33 (s,
3H); 1.34 (t, J=7.1, 3H); 0.94 (m, 1H); 0.34 (m, 2H); 0.18 (m,
2H).
Example A60
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid ethyl ester
[4072] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
5-ethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxo-
le (example A31) the title compound is obtained as colorless
solid.
[4073] MS (ESI): m/z=356 (MH.sup.+, 100%).
[4074] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.37 (s, 1H, --NH);
9.01 (s, 1H); 8.39 (s, 1H); 7.01 (d, J=8.6, 1H); 6.58 (d, J=8.6,
1H); 6.00 (s, 2H); 4.32 (qu, J=7.1, 2H); 3.95 (qu, J=6.9, 2H); 1.33
(t, J=7.1, 3H); 1.03 (t, J=6.9, 3H).
Example A61
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ethyl ester
[4075] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
5-propoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]diox-
ole (example A32) the title compound is obtained as colorless
solid.
[4076] MS (ESI): m/z=370 (MH.sup.+, 100%).
[4077] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.40 (s, 1H, --NH);
9.01 (s, 1H); 8.38 (d, J=3.5, 1H); 7.01 (d, J=8.6, 1H); 6.58 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.31 (qu, J=7.1, 2H); 3.84 (t, J=6.4,
2H); 1.42 (m, 2H); 1.33 (t, J=7.1, 3H); 0.61 (t, J=7.4, 3H).
Example A62
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid ethyl ester
[4078] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
5-butoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxo-
le (example A33) the title compound is obtained as colorless
solid.
[4079] MS (ESI): m/z=384 (MH.sup.+, 100%).
[4080] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.40 (s, 1H, --NH);
9.00 (s, 1H); 8.38 (s, 1H); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6,
1H); 6.00 (s, 2H); 4.31 (qu, J=7.1, 2H); 3.88 (t, J=6.3, 2H); 1.38
(m, 2H); 1.33 (t, J=7.1, 3H); 1.05 (m, 2H); 0.68 (t, J=7.4,
3H).
Example A63
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ethyl ester
[4081] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
5-(2-methoxy-ethoxy)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-ben-
zo[1,3]dioxole (example A34) the title compound is obtained as
colorless solid.
[4082] MS (ESI): m/z=386 (MH.sup.+, 100%); 372
(MH.sup.+--CH.sub.2).
[4083] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --NH);
9.01 (s, 1H); 8.39 (s, 1H); 7.02 (d, J=8.5, 1H); 6.61 (d, J=8.5,
1H); 6.01 (s, 1H); 4.31 (qu, J=7.1, 2H); 4.02 (t, J=4.6, 2H); 3.38
(t, J=4.6, 2H); 3.00 (s, 3H); 1.33 (t, J=7.1, 3H).
Example A64
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid ethyl ester
[4084] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
and
2-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]diox-
aborolane (example A43) the title compound is obtained as colorless
solid.
[4085] MS (ESI): m/z=372 (MH.sup.+, 100%); 358
(MH.sup.+--CH.sub.2).
[4086] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.87 (br.s, 1H, --NH);
8.98 (s, 1H); 8.33 (s, 1H); 7.65 (d, J=8.1, 1H); 6.77 (s, 1H); 6.75
(dd, J.sub.1=8.1, J.sub.2=2.2, 1H); 4.31 (qu, J=7.1, 2H); 4.21 (m,
2H); 3.87 (s, 3H); 3.52 (m, 2H); 3.10 (s, 3H); 1.33 (t, J=7.1,
3H).
Example A65
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid ethyl ester
[4087] Under an atmosphere of argon Pd(OAc).sub.2 (0.26 g; 1.14
mmol) and tricyclohexylphosphine (0.64 g; 2.28 mmol) is added to
oxygen free dioxane (117.0 mL). The mixture is stirred for 15 min
at ambient temperature. 2M Cs.sub.2CO.sub.2 solution in oxygen free
water (38.9 mL; 77.8 mmol) is added followed by
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
prepared according to the procedure described in US 2005/124623A1
(5.85 g; 25.95 mmol). The mixture is heated to 80.degree. C. before
addition of
2-(2-Cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-4,4,5,5-tetrame-
thyl-[1,3,2]dioxaborolane from example A44 (10.05 g; 28.53 mmol).
Afterwards the stirred reaction mixture is heated at 100.degree. C.
over night.
[4088] After addition of decolorizing charcoal (one spatula) the
cooled reaction mixture is filtered through a plug of celite. The
filtrate is concentrated under reduced pressure. The residue is
distributed between water (100 mL) and dichloromethane (250 mL).
The organic layer is separated the aqueous layer is extracted with
dichloromethane (2.times.50 mL) and the combined organic layers are
dried over MgSO.sub.4. The crud material is chromatographed on
silica gel (dichloromethane:MeOH/97:03) to give the title compound
as colorless solid after triturating with tert-BuOMe. Yield: 7.30
g.
[4089] MS (ESI): m/z=416 (MH.sup.+, 100%).
[4090] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.14 (br.s, 1H, --NH);
9.02 (s, 1H); 8.38 (d, J=3.3, 1H); 7.50 (d, J=11.5, 1H); 7.03 (d,
J=6.9, 1H); 5.40 (s, 2H); 4.32 (qu J=7.1, 2H); 3.88 (d, J=6.9, 2H);
3.47 (s, 3H); 1.34 (t, J=7.1, 3H); 0.95 (m, 1H); 0.35 (m, 2H); 0.20
(m, 2H).
[4091] The following compounds are obtained analogously to the
procedure described in the above example A65.
Example A66
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
[4092] Starting from
4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester
prepared according to the procedure described in US 2005/124623A1
and
2-[2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-4,4,5,5-
-tetramethyl-[1,3,2]-dioxabolane (example A45) the title compound
is obtained as colorless solid.
[4093] MS (ESI-): m/z=420 (MH.sup.-, 100%).
[4094] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.15 (br.s, 1H, --NH);
9.04 (s, 1H); 8.44 (d, J=3.5, 1H); 7.63 (d, J=9.7, 1H); 7.40 (t,
J=73.0, 1H); 7.18 (d, J=6.6, 1H); 4.32 (qu, J=7.1, 2H); 3.90 (d,
J=6.9, 2H); 1.33 (t, J=7.1, 3H); 0.94 (m, 1H); 0.35 (m, 2H); 0.20
(m, 2H).
Example A67
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4095]
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid ethyl ester (9.53 g; 25.0 mmol) from
example A48 is suspended in dioxane (170 mL) and water (100 mL).
After addition of LiOH (2.99 g; 125.0 mmol) the reaction mixture is
stirred at 100.degree. C. over night. The resulting solution is
evaporated to dryness. The residue is dissolved in hot
(60-90.degree. C.) water (250 mL) and pH is adjusted to 2-3 by
addition of 2M citric acid while still hot. After cooling to
ambient temperature the precipitated product is collected by
suction filtration, washed with water, ethanol and dried in high
vacuo at 50.degree. C. to yield 8.22 g of the title compound as
pale yellow solid.
[4096] MS (ESI): m/z=354 (MH.sup.+, 100%).
[4097] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
12.19 (br.s, 1H, --OH); 8.99 (s, 1H); 8.34 (d, J=3.4, 1H); 7.00 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 3.76 (d, J=6.7, 2H);
0.88 (m, 1H); 0.29 (m, 2H); 0.09 (m, 2H).
[4098] The following compounds are obtained analogously to the
procedure described in above example A67.
Example A68
4-(5-Cyclobutylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid
[4099]
4-(5-Cyclobutylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid ethyl ester (example A49) is used as
starting material to give the title compound as pale yellow
solid.
[4100] MS (ESI): m/z=324 (MH.sup.+--CO.sub.2, 100%); 256
(MH.sup.+--CO.sub.2--C.sub.5H.sub.8).
[4101] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --OH);
12.10 (br.s, 1H, --NH); 8.97 (s, 1H); 8.31 (d, J=3.2, 1H); 7.01 (d,
J=8.5, 1H); 6.58 (d, J=8.5, 1H); 6.00 (s, 2H); 3.83 (d, J=6.1, 2H);
2.38 (m, 1H); 1.67 (m, 3H); 1.49 (m, 3H).
Example A69
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid
[4102]
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid ethyl ester (example A60) was used as starting
material to give the title compound as pale yellow solid.
[4103] MS (ESI): m/z=356 (MH.sup.+, 100%).
[4104] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.37 (s, 1H, --NH);
9.01 (s, 1H); 8.39 (s, 1H); 7.01 (d, J=8.6, 1H); 6.58 (d, J=8.6,
1H); 6.00 (s, 2H); 4.32 (qu, J=7.1, 2H); 3.95 (qu, J=6.9, 2H); 1.33
(t, J=7.1, 3H); 1.03 (t, J=6.9, 3H).
Example A70
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid
[4105]
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid ethyl ester (example A61) was used as starting
material to give the title compound as pale yellow solid.
[4106] MS (ESI): m/z=342 (MH.sup.+, 100%).
[4107] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
12.19 (br.s, 1H, --OH); 8.98 (s, 1H); 8.33 (d, J=3.4, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 3.84 (t, J=6.4, 2H);
1.42 (m, 2H); 0.61 (t, J=7.4, 3H).
Example A71
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid
[4108]
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid ethyl ester (example A62) was used as starting
material to give the title compound as pale yellow solid.
[4109] MS (ESI): m/z=356 (MH.sup.+, 100%).
[4110] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
12.06 (br.s, 1H, --OH); 8.99 (s, 1H); 8.33 (d, J=2.3, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 3.89 (t, J=6.4, 2H);
1.48 (m, 2H); 1.03 (m, 2H); 0.68 (t, J=7.4, 3H).
Example A72
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4111]
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid ethyl ester (example A63) was used as
starting material to give the title compound as pale yellow
solid.
[4112] MS (ESI): m/z=358 (MH.sup.+, 100%).
[4113] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.22 (br.s, 2H, --NH
& --OH); 8.98 (s, 1H); 8.34 (s, 1H); 7.02 (d, J=8.6, 1H); 6.61
(d, J=8.6, 1H); 6.01 (s, 1H); 4.02 (t, J=4.7, 2H); 3.39 (t, J=4.7,
2H); 3.00 (s, 3H).
Example A73
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[4114]
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid ethyl ester (example A50) is used as starting
material to give the title compound as pale yellow solid.
[4115] MS (ESI): m/z=340 (MH.sup.+, 100%).
[4116] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.95 (br.s, 2H, --NH,
--OH); 8.96 (s, 1H); 8.28 (d, J=2.6, 1H); 7.59 (d, J=8.3, 1H); 6.72
(dd, J.sub.1=8.3, J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 3.91 (d,
J=6.9, 2H); 3.86 (s, 3H); 0.97 (m, 1H); 0.35 (m, 2H); 0.23 (m,
2H).
Example A74
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[4117]
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid ethyl ester (example A64) was used as starting
material to give the title compound as pale yellow solid.
[4118] MS (ESI): m/z=344 (MH.sup.+, 100%).
[4119] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.11 (br.s, 1H, .OH);
11.80 (br.s, 1H, --NH); 8.96 (s, 1H); 8.30 (d, J=3.4, 1H); 7.66 (d,
J=8.1, 1H); 6.77 (s, 1H); 6.75 (dd, J.sub.1=8.1, J.sub.2=2.2, 1H);
4.22 (t, J=4.6, 2H); 3.87 (s, 3H); 3.53 (t, J=4.6, 2H); 3.10 (s,
3H).
Example A75
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[4120]
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid ethyl ester (example A51) is used as starting
material to give the title compound as pale yellow solid.
[4121] MS (ESI): m/z=340 (MH.sup.+, 100%).
[4122] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.06 (br.s, 2H, --NH,
--OH); 9.01 (s, 1H); 8.31 (s, 1H); 7.17 (d, J=1.8, 1H); 7.11 (t,
J=1.8, 2H); 3.82 (d, J=6.8, 2H); 3.77 (s, 3H); 0.92 (m, 1H); 0.32
(m, 2H); 0.14 (m, 2H).
Example A76
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid
[4123]
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ethyl ester (example A52) is used as starting
material to give the title compound as pale yellow solid.
[4124] MS (ESI): m/z=328 (MH.sup.+ 100%).
[4125] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.10 (br.s, 2H, --NH,
--OH); 8.99 (s, 1H); 8.34 (s, 1H); 7.65 (dd, J.sub.1=8.4,
J.sub.2=7.0, 1H); 7.07 (dd, J.sub.1=11.5, J.sub.2=2.3, 1H); 6.95
(ddd, J.sub.1=J.sub.2=9.9, J.sub.3=2.3, 1H); 3.92 (d, J=7.0, 2H);
0.96 (m, 1H); 0.36 (m, 2H); 0.21 (m, 2H).
Example A77
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid
[4126]
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ethyl ester (example A53) is used as starting
material to give the title compound as pale yellow solid.
[4127] MS (ESI): m/z=328 (MH.sup.+, 100%).
[4128] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.15 (br.s, 2H, --NH,
--OH); 9.02 (s, 1H); 8.36 (s, 1H); 7.45-7.31 (m, 2H); 7.18 (dd,
J.sub.1=9.0, J.sub.2=5.4, 1H); 3.87 (d, J=6.1, 2H); 0.94 (m, 1H);
0.34 (m, 3H); 0.17 (m, 3H).
Example A78
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid
[4129]
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid ethyl ester (example A54) is used as starting material
to give the title compound as pale yellow solid.
[4130] MS (ESI): m/z=310 (MH.sup.+, 100%); 266
(MH.sup.+--CO.sub.2).
[4131] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.18 (br.s, 1H,
--NH/--OH); 12.09 (br.s, 1H, --NH/--OH); 9.01 (s, 1H); 8.32 (s,
1H); 7.62 (dd, J.sub.1=7.5, J.sub.2=1.5, 1H); 7.52 (ddd,
J.sub.1=8.4, J.sub.2=7.5, J.sub.3=1.5, 1H); 7.17 (d, J=8.4, 1H);
7.12 (d, J=7.5, 1H); 3.91 (d, J=6.9, 2H); 0.95 (m, 1H); 0.35 (m,
2H); 0.21 (m, 2H).
Example A79
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[4132]
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid ethyl ester (example A55) is used as
starting material to give the title compound as pale yellow
solid.
[4133] MS (ESI): m/z=358 (MH.sup.+, 100%); 314
(MH.sup.+--CO.sub.2).
[4134] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.04 (br.s, 2H, --NH,
--OH); 9.01 (s, 1H); 8.34 (s, 1H); 7.39 (d, J=9.8, 1H); 7.17 (d,
J=13.4, 1H); 4.84 (d, J=6.8, 2H & s, 3H); 0.93 (m, 1H); 0.33
(m, 2H); 0.16 (m, 2H).
Example A80
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[4135]
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid ethyl ester (example A56) is used as
starting material to give the title compound as pale yellow
solid.
[4136] MS (ESI): m/z=358.0 (MH.sup.+, 100%).
[4137] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.17 (br.s, 1H, --OH);
12.02 (br.s, 1H, --NH); 8.98 (s, 1H); 8.34 (s, 1H); 7.49 (d,
J=11.9, 1H); 6.92 (d, J=7.3, 1H); 3.97 (s, 3H); 3.95 (d, J=7.0,
2H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example A81
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid
[4138]
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ethyl ester (example A57) is used as starting
material to give the title compound as pale yellow solid.
[4139] MS (ESI): m/z=352 (MH.sup.+, 100%).
[4140] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.40 (s, 1H, --NH);
9.10 (s, 1H); 8.48 (d, J=3.0, 1H); 8.19 (d, J=2.0, 1H); 8.13 (dd,
J.sub.1=9.0, J.sub.2=3.0 1H); 7.27 (d, J=9.0, 1H); 4.00 (d, J=7.0,
2H); 2.60 (s, 3H); 0.95 (m); 0.37 (m, 2H); 0.23 (m, 2H).
Example A82
4-(5-Acetyl-4-methyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carboxylic acid
[4141]
4-(5-Acetyl-4-methyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid ethyl ester (example A58) is used as
starting material to give the title compound as pale yellow
solid.
[4142] MS (ESI): m/z=366 (MH.sup.+, 100%).
[4143] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.10 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=3.0, 1H); 8.10 (s, 1H); 7.10 (s, 1H); 4.00
(d, J=7.0 2H); 2.60 (s, 3H); 2.55 (s, 3H); 1.00 (m, 1H); 0.38 (m,
2H); 0.24 (m, 2H).
Example A83
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid
[4144]
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid ethyl ester (example A59) is used as starting
material to give the title compound as pale yellow solid.
[4145] MS (ESI): m/z=324 (MH.sup.+ 100%).
[4146] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.10 (br.s, 2H, --NH,
--OH); 8.99 (s, 1H); 8.30 (s, 1H); 7.43 (d, J=1.8, 1H); 7.32 (dd,
J.sub.1=8.4 J.sub.2=1.8, 1H); 7.06 (d, J=8.4, 1H); 3.86 (d, J=6.9,
2H); 2.33 (s, 3H); 0.94 (m, 1H); 0.33 (m, 2H); 0.18 (m, 2H).
Example A84
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid
[4147] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid ethyl ester (example A65) the title
compound is obtained as color-less solid.
[4148] MS (ESI): m/z=388 (MH.sup.+, 100%).
[4149] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.06 (br.s, 2H, --NH,
--OH); 8.98 (s, 1H); 8.33 (s, 1H); 7.49 (d, J=11.5, 1H); 7.02 (d,
J=7.1, 1H); 5.39 (s, 2H); 3.87 (d, J=6.9, 2H); 3.47 (s, 3H); 0.94
(m, 1H); 0.34 (m, 2H); 0.20 (m, 2H).
Example A85
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid
[4150] Starting from
4-[2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid ethyl ester (example A66)
the title compound is obtained as color-less solid.
[4151] MS (ESI): 394 (MH.sup.+, 100%).
[4152] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): .sup.1H-NMR (300 MHz,
DMSO-d.sub.6): 12.16 (br.s, 2H, --NH, --OH); 9.02 (s, 1H); 8.38 (s,
1H); 7.63 (d, J=10.8, 1H); 7.40 (t, J=73.2, 1H); 7.18 (d, J=6.9,
1H); 3.90 (d, J=6.9, 2H); 0.95 (m, 1H); 0.35 (m, 2H); 0.20 (m,
2H).
Example A86
4-({1-[4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid
tert-butyl ester
[4153] To a suspension of
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (3.53 g; 10.0 mmol) from example A67 in dry
dichloromethane (50 mL) is added
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12.0
mmol), triethylamine (15.0 mmol) and 1-hydroxybenzotriazole (10.0
mmol). The suspension is stirred at ambient temperature for one
hour. To the resulting solution, 4-amino-piperidine-1-carboxylic
acid tert-butyl ester (12.0 mmol) is added and stirring is
continued overnight at ambient temperature. The reaction mixture is
loaded onto a silica gel column and purified by flash
chromatography using acetic acid ethyl ester/2-propanol (98:2 v/v).
The eluate containing the product fraction is collected and
evaporated. The product is triturated with n-hexane and dried in
high vacuo at 50.degree. C. to yield 3.85 g of the title compound
as white solid.
[4154] MS (ESI): m/z=558 (MNa.sup.+); 536 (MH.sup.+, 100%); 480
(MH.sup.+--C.sub.4H.sub.8).
[4155] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (s, 1H, --NH);
9.03 (s, 1H); 8.44 (d, J=7.7, 1H, --NH); 8.29 (d, J=3.2, 1H); 7.01
(d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.07 (m, 1H);
3.87 (.about.d, J 13.5, 2H); 3.76 (d, J=6.8, 2H); 1.94 (.about.dd,
J.sub.1 .about.12.8, J.sub.2 .about.3.4, 2H); 1.46 (m, 2H); 1.42 (s
9H); 0.87 (m, 1H); 0.27 (m, 2H); 0.12 (m, 2H).
[4156] The following compounds are obtained analogously to the
procedure described in above example A86.
Example A87
trans-(4-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4157] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4158] MS (ESI): m/z=550 (MH.sup.+, 100%); 494
(MH.sup.+--C.sub.4H.sub.8).
[4159] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.26 (br.s, 1H, --NH);
9.02 (s, 1H); 8.29 (d, J=8.1, 1H, --NH); 8.27 (s, 1H); 7.00 (d,
J=8.6, 1H); 6.74 (d, J=7.7, 1H, --NH); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 3.76 (d, J=6.7, 2H & m, 1H); 1.99 (m, 2H); 1.85 (m,
2H); 1.39 (s, 9H); 1.43-1.26 (m, 4H); 0.85 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example A88
cis-(4-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4160] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4161] MS (ESI): m/z=550 (MH.sup.+, 100%); 494
(MH.sup.+--C.sub.4H.sub.8); 450
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4162] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.06 (s, 1H); 8.60 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.00 (d,
J=8.6, 1H); 6.94 (d, J=6.7, 1H, --NH); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 4.02 (m, 1H); 3.77 (d, J=6.7, 2H); 3.45 (m, 1H); 1.78 (m,
2H); 1.69-1.56 (m, 6H); 1.39 (s, 9H); 0.86 (m, 1H); 0.30 (m, 2H);
0.11 (m, 2H).
Example A89
(S)-3-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester
[4163] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
(S)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
[4164] MS (ESI): m/z=522 (MH.sup.+, 100%); 466
(MH.sup.+--C.sub.4H.sub.8).
[4165] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 1H); 8.55 (d, J=6.9, 1H, --NH); 8.31 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01 (s, 2H); 4.50 (m, 1H); 3.76
(d, J=6.7, 2H); 3.64 (m, 1H); 3.44 (m, 2H); 3.24 (m, 2H); 2.21 (m,
1H); 1.96 (m, 1H); 1.42 (s, 9H); 0.87 (m, 1H); 0.29 (m, 2H); 0.11
(m, 2H).
Example A90
(R)-3-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester
[4166] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
(R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
[4167] MS (ESI): m/z=522 (MH.sup.+, 100%); 466
(MH.sup.+--C.sub.4H.sub.8).
[4168] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 1H); 8.55 (d, J=6.9, 1H, --NH); 8.31 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01 (s, 2H); 4.50 (m, 1H); 3.76
(d, J=6.7, 2H); 3.64 (m, 1H); 3.44 (m, 2H); 3.24 (m, 2H); 2.21 (m,
1H); 1.96 (m, 1H); 1.42 (s, 9H); 0.87 (m, 1H); 0.29 (m, 2H); 0.11
(m, 2H).
Example A91
4-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-piperidine-1-carboxylic acid
tert-butyl ester
[4169] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
4-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
Example A92
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]amino}-methyl)-piperidine-1-carboxylic acid
tert-butyl ester
[4170] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
3-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
Example A93
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid
tert-butyl ester
[4171] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
3-aminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
Example A94
2-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid
tert-butyl ester
[4172] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
2-aminomethyl-morpholine-4-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
Example A95
2-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid
tert-butyl ester
[4173] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and 3-amino-azetidine-1-carboxylic
acid tert-butyl ester the title compound is obtained as colorless
solid.
Example A96
(S)-3-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester
[4174] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
(S)-3-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
Example A97
(R)-3-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester
[4175] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A67) and
(R)-3-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
Example A98
4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester
[4176] Starting from
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A73) and 4-amino-piperidine-1-carboxylic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4177] MS (ESI): m/z=522 (MH.sup.+, 100%); 466
(MH.sup.+--C.sub.4H.sub.8); 422
(MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4178] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.89 (br.s, 1H, --NH);
9.00 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.62 (d,
J=8.3, 1H); 6.72 (dd, J.sub.1=8.3, J.sub.2=2.2, 1H); 6.69 (d,
J=2.2, 1H & br.s, 1H, --NH); 3.92 (d, J=6.8, 2H); 3.86 (s, 3H
& m, 2H); 3.03 (m, 2H); 1.94 (m, 2H); 1.42 (m, 4H & s, 9H);
0.97 (m, 1H); 0.35 (m, 2H); 0.24 (m, 2H).
Example A99
cis-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4179] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A73) and cis-(4-amino-cyclohexyl)-carbamic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4180] MS (ESI): m/z=536 (MH.sup.+, 100%); 480
(MH.sup.+--C.sub.4H.sub.8); 436
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4181] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.88 (br.s, 1H, --NH);
9.03 (s, 1H); 8.68 (d, J=7.7, 1H, --NH); 8.20 (s, 1H); 7.62 (d,
J=8.3, 1H); 6.92 (br.s, 1H, --NH); 6.72 (dd, J.sub.1=8.3,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 4.04 (m, 1H); 3.92 (d,
J=6.9, 2H); 3.86 (s, 3H); 3.45 (m, 1H); 1.90-1.48 (m, 8H); 1.40 (s,
9H); 0.98 (m, 1H); 0.35 (m, 2H); 0.24 (m, 2H).
Example A100
trans-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4182] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A73) and
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4183] MS (ESI): m/z=536 (MH.sup.+, 100%); 480
(MH.sup.+--C.sub.4H.sub.8).
[4184] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.89 (br.s, 1H, --NH);
9.00 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.19 (s, 1H); 7.62 (d,
J=8.3, 1H); 6.92 (br.s, 1H, --NH); 6.72 (dd, J.sub.1=8.3,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 3.91 (d, J=6.9, 2H); 3.86
(s, 3H); 3.78 (m, 1H); 3.28 (m, 1H); 2.00 (m, 2H); 1.86 (m, 2H);
1.34 (m, 4H & s, 9H); 0.97 (m, 1H); 0.34 (m, 2H); 0.24 (m,
2H).
Example A101
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4185] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A75) and
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4186] MS (ESI): m/z=536 (MH.sup.+, 100%); 480
(MH.sup.+--C.sub.4H.sub.8).
[4187] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.05 (s, 1H); 8.34 (d, J=7.7, 1H, --NH); 8.23 (s, 1H); 7.20 (t,
J=1.6, 1H); 7.12 (d, J=1.6, 2H); 6.74 (d, J=7.7, 1H, --NH); 3.87
(d, J=6.9, 2H); 3.77 (s, 3H &m, 1H); 3.31 (m, 1H); 2.00 (m,
2H); 1.85 (m, 2H); 1.43-1.22 (m, 4H); 1.39 (s, 9H); 0.84 (m, 1H);
0.32 (m, 2H); 0.15 (m, 2H).
Example A102
cis-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4188] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A75) and cis-(4-amino-cyclohexyl)-carbamic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4189] MS (ESI): m/z=536 (MH.sup.+, 100%); 480
(MH.sup.+--C.sub.4H.sub.8).
[4190] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.08 (s, 1H); 8.65 (d, J=7.7, 1H, --NH); 8.24 (d, J=3.3, 1H); 7.19
(t, J=1.6, 1H); 7.11 (d, J=1.6, 2H); 6.95 (d, J=6.1, 1H, --NH);
4.04 (m, 1H); 3.83 (d, J=6.8, 2H); 3.78 (s, 3H); 3.45 (m, 1H); 1.79
(m, 2H); 1.70-1.56 (m, 6H); 1.40 (s, 9H); 0.90 (m, 1H); 0.33 (m,
2H); 0.16 (m, 2H).
Example A103
4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester
[4191] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A75) and 4-amino-piperidine-1-carboxylic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4192] MS (ESI): m/z=522 (MH.sup.+, 100%); 466
(MH.sup.+--C.sub.4H.sub.8).
[4193] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.05 (s, 1H); 8.50 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.19 (t,
J=1.7, 1H); 7.11 (d, J=1.7, 2H); 4.09 (m, 1H); 3.86 (m, 2H); 3.83
(d, J=6.9, 2H); 3.77 (s, 3H); 3.04 (m, 2H); 1.94 (m, 2H); 1.47 (m,
2H); 1.43 (s, 9H); 0.93 (m, 1H); 0.32 (m, 2H); 0.15 (m, 2H).
Example A104
trans-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4194] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A76) and trans-(4-amino-cyclohexyl)-carbamic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4195] MS (ESI): m/z=524 (MH.sup.+, 100%); 468
(MH.sup.+--C.sub.4H.sub.8); 424
(MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4196] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.06 (s, 1H); 8.34 (d, J=7.9, 1H; --NH); 8.26 (s, 1H); 7.67 (dd,
J.sub.1=8.4, J.sub.2=7.2, 1H); 7.08 (dd, J.sub.1=11.6, J.sub.2=2.4,
1H); 6.96 (ddd, J.sub.1=J2=8.5, J.sub.3=2.4, 1H); 6.72 (d, J=7.6,
1H, --NH); 3.92 (d, J=7.0, 2H); 3.79 (m, 1H); 3.13 (m, 1H); 2.00
(m, 2H); 1.85 (m, 2H); 1.39 (s, 9H & m, 4H); 0.96 (m, 1H); 0.36
(m, 2H); 0.22 (m, 2H).
Example A105
cis-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4197] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A76) and cis-(4-amino-cyclohexyl)-carbamic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4198] MS (ESI): m/z=524 (MH.sup.+, 100%); 468
(MH.sup.+--C.sub.4H.sub.8); 424
(MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4199] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.06 (s, 1H); 8.65 (d, J=7.7, 1H; --NH); 8.26 (d, J=2.0, 1H); 7.67
(dd, J.sub.1=8.5, J.sub.2=7.0, 1H); 7.08 (dd, J.sub.1=11.6,
J.sub.2=2.4, 1H); 6.96 (ddd, J=J.sub.2=8.5, J.sub.3=2.4, 1H); 6.91
(br.s, 1H, --NH); 4.05 (m, 1H); 3.92 (d, J=7.0, 2H); 3.45 (m, 1H);
1.79 (m, 2H); 1.73-1.51 (m, 6H); 1.40 (s, 9H); 0.97 (m, 1H); 0.36
(m, 2H); 0.22 (m, 2H).
Example A106
4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4200] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A76) and 4-amino-piperidine-1-carboxylic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4201] MS (ESI): m/z=510 (MH.sup.+); 454 (MH.sup.+--C.sub.4H.sub.8.
100%); 410 (MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4202] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.07 (br.s, 1H, --NH);
9.03 (s, 1H); 8.49 (d, J=7.8, 1H; --NH); 8.29 (d, J=2.4, 1H); 7.67
(dd, J.sub.1=8.5, J.sub.2=7.0, 1H); 7.08 (dd, J.sub.1=11.6,
J.sub.2=2.4, 1H); 6.96 (ddd, J.sub.1=J.sub.2=8.5, J.sub.3=2.4, 1H);
4.06 (m, 2H); 3.92 (d, J=7.0, 2H); 3.87 (m, 1H); 3.03 (m, 2H); 1.94
(m, 2H); 1.44 (m, 2H); 1.42 (s, 9H); 0.96 (m, 1H); 0.36 (m, 2H);
0.22 (m, 2H).
Example A107
trans-(4-{[4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4203] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A77) and trans-(4-amino-cyclohexyl)-carbamic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4204] MS (ESI): m/z=524 (MH.sup.+, 100%); 468
(MH.sup.+--C.sub.4H.sub.8).
[4205] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.08 (br.s, 1H, --NH);
9.06 (s, 1H); 8.33 (d, J=7.9, 1H, --NH); 8.28 (d, J=3.0, 1H);
7.45-7.34 (m, 2H); 7.18 (dd, J.sub.1=9.1, J.sub.2=4.5, 1H); 6.72
(d, J=7.3, 1H, --NH); 3.88 (d, J=6.9, 2H); 3.79 (m, 1H); 3.29 (m,
1H); 2.00 (m, 2H); 1.85 (m, 2H); 1.39 (s, 9H & m, 4H); 0.94 (m,
1H); 0.33 (m, 2H); 0.18 (m, 2H).
Example A108
4-{[4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4206] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A77) and 4-amino-piperidine-1-carboxylic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4207] MS (ESI): m/z=510 (MH.sup.+, 100%); 454
(MH.sup.+--C.sub.4H.sub.8); 410
(MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4208] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.11 (br.s, 1H, --NH);
9.06 (s, 1H); 8.37 (d, J=3.4, 1H); 8.48 (d, J=7.8, 1H, --NH); 8.30
(s, 1H); 7.46-7.34 (m, 2H); 7.19 (dd, J.sub.1=9.1, J.sub.2=4.4,
1H); 4.09 (m, 1H); 3.88 (d, J=6.9, 2H & m, 2H); 3.03 (m, 2H);
1.94 (m, 2H); 1.46 (m, 2H); 1.42 (s, 9H); 0.94 (m, 1H); 0.34 (m,
2H); 0.18 (m, 2H).
Example A109
trans-(4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester
[4209] Starting from
4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (example A78) and trans-(4-amino-cyclohexyl)-carbamic acid
tert-butyl ester the title compound is obtained as colorless
solid.
[4210] MS (ESI): m/z=506 (MH.sup.+, 100%); 450
(MH.sup.+--C.sub.4H.sub.8).
[4211] .sup.1H-NMR (3000 MHz, DMSO-d.sub.6): 12.02 (s, 1H, --NH);
9.05 (s, 1H); 8.34 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.63 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J2=7.6, J.sub.3=0.9, 1H); 6.73 (d, J=7.5, 1H, --NH);
3.91 (d, J=6.9, 2H); 3.78 (m, 1H); 3.41 (m, 1H); 2.00 (m, 2H); 1.86
(m, 2H); 1.40 (s, 9H); 1.34 (m, 4H); 0.97 (m, 1H); 0.34 (m, 2H);
0.21 (m, 2H).
Example A110
4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbonyl-
]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4212] Starting from
4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (example A78) and 4-amino-piperidine-1-carboxylic acid
tert-butyl ester the title compound is obtained as colorless
solid.
[4213] MS (ESI): m/z=492 (MH.sup.+, 100%); 436
(MH.sup.+--C.sub.4H.sub.8).
[4214] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.06 (s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.63 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 4.09 (m, 1H); 3.91 (d,
J=6.9, 2H); 3.88 (m, 2H); 3.04 (m, 1H); 1.93 (m, 2H); 1.47 (m, 2H);
1.42 (s, 9H); 0.96 (m, 1H); 0.34 (m, 2H); 0.21 (m, 2H).
Example A111
4-{[4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester
[4215] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A79) and
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4216] MS (ESI): m/z=540 (MH.sup.+, 100%); 484
(MH.sup.+--C.sub.4H.sub.8).
[4217] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.02 (br.s, 1H, --NH);
9.05 (s, 1H); 8.49 (d, J=7.8, 1H, --NH); 8.28 (s, 1H); 7.41 (d,
J=9.8, 1H); 7.18 (d, J=13.3, 1H); 4.09 (m, 1H); 3.98 (m, 2H); 3.85
(s, 3H); 3.84 (d, J=6.7, 2H); 3.03 (m, 1H); 1.96 (m, 2H); 1.46 (m,
2H); 1.42 (s, 9H); 0.93 (m, 1H); 0.34 (m, 2H); 0.17 (m, 2H).
Example A112
(R)-3-{[4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester
[4218] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A79) and
(R)-3-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4219] MS (ESI): m/z=540 (MH.sup.+, 100%); 484
(MH.sup.+--C.sub.4H.sub.8); 440
(MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4220] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.02 (br.s, 1H, --NH);
9.02 (s, 1H); 8.58 (d, J=7.9, 1H, --NH); 8.30 (s, 1H); 7.41 (d,
J=9.9, 1H); 7.19 (d, J=13.4, 1H); 3.99 (m, 1H); 3.88 (s, 3H &
d, J=6.8, 2H); 3.62 (m, 1H); 3.38 (m, 3H); 1.92 (m, 1H); 1.72 (m,
2H); 1.53 (m, 1H); 1.29 (br.s, 9H); 0.92 (m, 1H); 0.32 (m, 2H);
0.18 (m, 2H).
Example A113
(R)-3-{[4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester
[4221] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A79) and
(R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
[4222] MS (ESI): m/z=526 (MH.sup.+, 100%); 470
(MH.sup.+--C.sub.4H.sub.8).
[4223] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.06 (br.s, 1H, --NH);
9.04 (s, 1H); 8.60 (d, J=6.9, 1H, --NH); 8.31 (d, J=2.2, 1H); 7.41
(d, J=9.9, 1H); 7.18 (d, J=13.4, 1H); 4.51 (m, 1H); 3.85 (s, 3H
& d, J=6.7, 2H); 3.62 (m, 1H); 3.44 (m, 2H); 3.26 (m, 1H); 2.22
(m, 1H); 1.99 (m, 2H); 1.42 (s, 9H); 0.93 (m, 1H); 0.34 (m, 2H);
0.17 (m, 2H).
Example A114
trans-(4-{[4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid
tert-butyl ester
[4224] Starting from
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A80) and
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4225] MS (ESI): m/z=554 (MH.sup.+, 100%); 498
(MH.sup.+--C.sub.4H.sub.8).
[4226] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.96 (br.s, 1H, --NH);
9.01 (s, 1H); 8.35 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.49 (d,
J=11.8, 1H); 6.92 (d, J=7.3, 1H); 6.74 (d, J=7.8, 1H, --NH); 3.97
(s, 1H); 3.94 (d, J=7.0, 2H); 3.77 (m, 1H); 1.99 (m, 2H); 1.85 (m,
2H); 1.43-1.24 (m, 4H); 1.39 (s, 9H); 0.96 (m, 1H); 0.36 (m, 2H);
0.22 (m, 2H).
Example A115
4-{[4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]py-
rimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester
[4227] Starting from
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A80) and
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4228] MS (ESI): m/z=540 (MH.sup.+, 100%); 484
(MH.sup.+--C.sub.4H.sub.8).
[4229] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.97 (br.s, 1H, --NH);
9.01 (s, 1H); 8.50 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.49 (d,
J=11.8, 1H); 6.93 (d, J=7.3, 1H); 4.07 (m, 1H); 3.97 (s, 1H); 3.95
(d, J=7.3, 2H); 3.87 (m, 1H); 3.03 (m, 2H); 1.93 (m, 2H); 1.46 (m,
2H); 1.42 (s, 9H); 0.97 (m, 1H); 0.36 (m, 2H); 0.21 (m, 2H).
Example A116
(R)-3-{[4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester
[4230] Starting from
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A80) and
(R)-3-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4231] MS (ESI): m/z=540 (MH.sup.+, 100%); 484
(MH.sup.+--C.sub.4H.sub.8); 440
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4232] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 11.97 (br.s, 1H,
--NH); 8.98 (s, 1H); 8.59 (d, J=7.8, 1H, --NH); 8.28 (s, 1H); 7.50
(d, J=11.9, 1H); 6.93 (d, J=7.3, 1H); 3.97 (s, 3H & m, 1H);
3.95 (d, J=7.0, 2H); 3.63 (m, 1H); 3.36 (m, 3H); 1.91 (m, 2H); 1.73
(m, 2H); 1.55 (m, 1H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example A117
(S)-3-{[4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester
[4233] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A80) and
(S)-3-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4234] MS (ESI): m/z=540 (MH.sup.+, 100%); 484
(MH.sup.+--C.sub.4H.sub.8); 440
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4235] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 11.97 (br.s, 1H,
--NH); 8.98 (s, 1H); 8.59 (d, J=7.8, 1H, --NH); 8.28 (s, 1H); 7.50
(d, J=11.9, 1H); 6.93 (d, J=7.3, 1H); 3.97 (s, 3H & m, 1H);
3.95 (d, J=7.0, 2H); 3.63 (m, 1H); 3.36 (m, 3H); 1.91 (m, 2H); 1.73
(m, 2H); 1.55 (m, 1H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example A118
(R)-3-{[4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester
[4236] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (example A80) and
(R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound is obtained as colorless solid.
[4237] MS (ESI): m/z=548 (MNa.sup.+); 526 (MH.sup.+, 100%).
[4238] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.00 (s, 1H); 8.61 (d, J=6.9, 1H; --NH); 8.28 (s, 1H); 7.50 (d,
J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.51 (m, 1H); 3.96 (s, 3H); 3.95
(d, J=7.1, 2H); 3.61 (m, 1H); 3.43 (m, 2H); 3.24 (m, 1H); 2.21 (m,
1H); 1.96 (m, 1H); 1.42 (s, 9H); 0.97 (m, 1H); 0.36 (m, 2H), 0.21
(m, 2H).
Example A119
4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4239] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A83) and 4-amino-piperidine-1-carboxylic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4240] MS (ESI): m/z=506 (MH.sup.+, 100%); 450
(MH.sup.+--C.sub.4H.sub.8).
[4241] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.03 (s, 1H); 8.50 (d, J=7.7, 1H, --NH); 8.24 (s, 1H); 7.44 (d,
J=2.0, 1H); 7.33 (dd, J.sub.1=8.4, J.sub.2=2.0, 1H); 7.06 (d,
J=8.4, 1H); 4.09 (m, 1H); 3.86 (d, J=6.9, 2H & m, 2H); 3.04 (m,
2H); 2.33 (s, 3H); 1.94 (m, 2H); 1.46 (m, 2H); 1.43 (s, 9H); 0.94
(m, 1H); 0.33 (m, 2H); 0.19 (m, 2H).
Example A120
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester
[4242] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A83) and trans-(4-amino-cyclohexyl)-carbamic
acid tert-butyl ester the title compound is obtained as colorless
solid.
[4243] MS (ESI): m/z=520 (MH.sup.+, 100%); 464
(MH.sup.+--C.sub.4H.sub.8).
[4244] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.03 (s, 1H); 8.35 (d, J=7.8, 1H, --NH); 8.21 (s, 1H); 7.44 (s,
1H); 7.33 (d, J=8.4, 1H); 7.06 (d, J=8.4, 1H); 6.72 (d, J=7.3, 1H,
--NH); 3.86 (d, J=6.9, 2H); 3.77 (m, 1H); 3.29 (m, 1H); 2.33 (s,
3H); 2.00 (m, 2H); 1.85 (m, 2H); 1.44-1.23 (m, 4H); 1.39 (s, 9H);
0.94 (m, 1H); 0.33 (m, 2H); 0.18 (m, 2H).
Example A121
trans-[4-({1-[4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
tert-butyl ester
[4245] Starting from
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A68) and
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4246] MS (ESI): m/z=564 (MH.sup.+); 508
(MH.sup.+--C.sub.4H.sub.8).
[4247] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.02 (s, 1H); 8.28 (d, J=7.9, 1H, --NH); 8.24 (d, J=3.2, 1H); 7.50
(s, 1H); 7.02 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H);
4.30 (m, 1H); 3.76 (d, J=6.8, 2H); 3.50 (m, 1H); 3.30 (m, 1H); 2.30
(m, 2H); 2.00 (m, 2H); 0.95 (m, 1H); 0.30 (m, 2H); 0.10 (m,
2H).
Example A122
4-({1-[4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midin-7-yl]methanoyl}-amino)-piperidine-1-carboxylic acid
tert-butyl ester
[4248] Starting from
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A68) and
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound is obtained as colorless solid.
[4249] MS (ESI): m/z=550 (MH.sup.+); 494
(MH.sup.+--C.sub.4H.sub.8); 450
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4250] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --NH);
9.02 (s, 1H); 8.42 (d, J=7.7, 1H, --NH); 8.28 (d, J=1.8, 1H); 7.01
(d, J=8.6, 1H); 6.72 (d, J=7.5, 1H, --NH); 6.59 (d, J=8.6, 1H);
6.01 (s, 2H); 3.85 (d, J=6.2, 2H); 3.77 (m, 1H); 3.30 (m, 1H); 2.38
(m, 1H); 2.00 (m, 2H); 1.85 (m, 2H); 1.67 (m, 3H); 1.50 (m, 3H);
1.40 (s, 9H); 1.34 (m, 4H).
Example A123
4-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
nyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4251] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (example A69) and commercially available
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4252] MS (ESI): m/z=510 (MH.sup.+, 100%); 454
(MH.sup.+--C.sub.4H.sub.8).
[4253] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (s, 1H, --NH);
9.02 (s, 1H); 8.43 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.07 (m, 1H); 3.96
(qu, J=7.0, 2H); 3.87 (m, 2H); 3.03 (m, 2H); 1.92 (m, 2H); 1.43 (m,
2H & s, 9H); 1.03 (t, J=7.0, 3H).
Example A124
(R)-3-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester
[4254] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (example A69) and commercially available
(R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound was obtained as colorless solid.
[4255] MS (ESI): m/z=496 (MH.sup.+, 100%); 440
(MH.sup.+--C.sub.4H.sub.8).
[4256] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.32 (s, 1H, --NH);
9.02 (s, 1H); 8.56 (d, J=6.9, 1H, --NH); 8.32 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.52 (m, 1H); 3.96
(qu, J=6.9, 2H); 3.62 (m, 1H); 3.50-3.37 (m, 2H); 3.25 (m, 1H);
2.22 (m, 1H); 1.98 (m, 2H); 1.42 (s, 9H); 1.04 (t, J=6.9, 3H).
Example A125
4-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4257] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (example A70) and commercially available
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4258] MS (ESI): m/z=524 (MH.sup.+, 100%); 468
(MH.sup.+--C.sub.4H.sub.8).
[4259] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
9.02 (s, 1H); 8.43 (d, J=7.8, 1H, --NH); 7.95 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.04 (m, 1H); 3.85
(t, J=6.4, 2H & m, 2H); 3.03 (m, 2H); 1.97 (m, 2H); 1.52-1.37
(s, 9H & m, 4H); 0.61 (t, J=7.4, 3H).
Example A126
(R)-3-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester
[4260] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (example A70) and commercially available
(R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound was obtained as colorless solid.
[4261] MS (ESI): m/z=510 (MH.sup.+, 100%); 454
(MH.sup.+--C.sub.4H.sub.8).
[4262] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.34 (s, 1H, --NH);
9.01 (s, 1H); 8.55 (d, J=6.9, 1H, --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.01 (s, 2H); 4.51 (m, 1H); 3.85
(t, J=6.4, 2H); 3.62 (m, 1H); 3.42 (m, 2H); 3.24 (m, 1H); 2.21 (m,
1H); 1.98 (m, 1H); 1.42 (s, 9H & m, 2H); 0.62 (t, J=7.4,
3H).
Example A127
4-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
nyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
[4263] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (example A71) and commercially available
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4264] MS (ESI): m/z=538 (MH.sup.+, 100%); 482
(MH.sup.+--C.sub.4H.sub.8).
[4265] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 1H); 8.43 (d, J=7.8, 1H, --NH); 8.28 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.07 (m, 1H); 3.88
(t, J=6.4, 2H & m, 2H); 3.03 (m, 2H); 1.94 (m, 2H); 1.52-1.34
(m, 4H); 1.42 (s, 9H); 1.04 (m, 2H); 0.69 (t, J=7.4, 3H).
Example A128
3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
nyl]-amino}-1-carboxylic acid tert-butyl ester
[4266] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (example A70) and commercially available
3-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4267] MS (ESI): m/z=538 (MH.sup.+, 100%); 482
(MH.sup.+--C.sub.4H.sub.8).
[4268] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.00 (s, 1H); 8.54 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 3.99 (m, 1H); 3.88
(t, J=6.4, 2H); 3.61 (m, 2H); 3.38 (m, 2H); 1.92 (m, 1H); 1.72 (m,
2H); 1.56 (m, 2H); 1.38 (m, 2H); 1.28 (br.s, 9H); 1.04 (m, 2H);
0.69 (t, J=7.4, 3H).
Example A129
(R)-3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arbonyl]amino}-pyrrolidine-1-carboxylic acid tert-butyl ester
[4269] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (example A71) and commercially available
(R)-3-amino-pyrrolidine-1-carboxylic acid tert-butyl ester the
title compound was obtained as colorless solid.
[4270] MS (ESI): m/z=524 (MH.sup.+, 100%); 468
(MH.sup.+--C.sub.4H.sub.8).
[4271] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 12.33 (br.s, 1H, --NH);
9.01 (s, 1H); 8.54 (d, J=6.9, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.01 (m, 1H); 3.89
(t, J=6.4, 2H); 3.62 (m, 1H); 3.43 (m, 2H); 3.26 (m, 1H); 2.21 (m,
1H); 1.98 (m, 1H); 1.43 (s, 9H); 1.39 (m, 2H); 1.05 (m, 2H); 0.69
(t, J=7.4, 3H).
Example A130
trans-[4-({4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl
ester
[4272] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A74) and commercially available
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4273] MS (ESI): m/z=540 (MH.sup.+); 484
(MH.sup.+--C.sub.4H.sub.8).
[4274] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.00 (s, 1H); 8.38 (d, J=7.7, 1H, --NH); 8.22 (d, J=3.1, 1H); 7.69
(d, J=8.2, 1H); 6.77 (s, 1H); 6.75 (dd, J.sub.1=8.2, J.sub.2=2.2,
1H); 6.71 (d, J=7.5, 1H, --NH); 4.23 (t, J=4.6, 2H); 3.87 (s, 3H);
3.77 (m, 1H); 3.54 (t, J=4.6, 2H); 3.31 (m, 1H); 3.13 (s, 3H); 1.99
(m, 2H); 1.85 (m, 2H); 1.39 (s, 9H); 1.33 (m, 4H).
Example A131
cis-[4-({4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl
ester
[4275] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A74) and commercially available
cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4276] MS (ESI): m/z=540 (MH+); 484 (MH.sup.+--C.sub.4H.sub.8); 440
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4277] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.03 (s, 1H); 8.69 (d, J=7.7, 1H, --NH); 8.22 (d, J=3.3, 1H); 7.69
(d, J=8.3, 1H); 6.93 (br.s, 1H, --NH); 6.77 (s, 1H); 6.76 (d,
J=8.3, 1H); 4.24 (t, J=4.6, 2H); 4.04 (br.s, 1H); 3.87 (s, 3H);
3.55 (t, J=4.6, 2H); 3.44 (br.s, 1H); 3.13 (s, 3H); 1.77 (m, 2H);
1.63 (m, 4H+2H); 1.40 (s, 9H).
Example A132
4-({4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl}-amino)piperidine-1-carboxylic acid tert-butyl ester
[4278] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A74) and commercially available
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4279] MS (ESI): m/z=548 (MNa.sup.+); 526 (MH.sup.+); 470
(MH.sup.+--C.sub.4H.sub.8).
[4280] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.76 (br.s, 1H, --NH);
9.00 (s, 1H); 8.53 (d, J=7.8, 1H, --NH); 8.24 (d, J=3.3, 1H); 7.69
(d, J=8.3, 1H); 6.77 (s, 1H); 6.75 (dd, J.sub.1=8.3, J.sub.2=2.2,
1H); 4.23 (t, J=4.6, 2H); 4.06 (m, 1H); 3.87 (s, 3H+m, 2H); 3.54
(t, J=4.6, 2H); 3.13 (s, 3H); 3.03 (m, 2H); 1.93 (m, 2H); 1.42 (s,
9H+m, 2H).
Example A133
trans-[4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d-
]pyrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl
ester
[4281] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (example A72) and commercially available
trans-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4282] MS (ESI): m/z=554 (MH.sup.+, 100%); 498
(MH.sup.+--C.sub.4H.sub.8).
[4283] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.20 (br. s, 1H,
--NH); 9.02 (s, 1H); 8.28 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.02
(d, J=8.6, 1H); 6.93 (d, J=7.6, 1H, --NH); 6.62 (d, J=8.6, 1H);
6.02 (s, 2H); 4.04 (t, J=4.7, 2H & m, 1H); 3.44 (m, 1H); 3.40
(t, J=4.7, 2H); 3.03 (s, 3H); 1.90-1.56 (m, 8H); 1.40 (s, 9H).
Example A134
cis-[4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl
ester
[4284] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (example A72) and commercially available
cis-(4-amino-cyclohexyl)-carbamic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4285] MS (ESI): m/z=554 (MH.sup.+, 100%); 498
(MH.sup.+--C.sub.4H.sub.8); 454
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4286] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.21 (br. s, 1H,
--NH); 9.05 (s, 1H); 8.60 (d, J=7.8, 1H, --NH); 8.28 (d, J=3.3,
1H); 7.02 (d, J=8.6, 1H); 6.72 (d, J=7.6, 1H, --NH); 6.61 (d,
J=8.6, 1H); 6.01 (s, 2H); 4.03 (t, J=4.7, 2H); 3.78 (m, 1H); 3.38
(t, J=4.7, 2H); 3.30 (m, 1H); 3.02 (s, 3H); 2.00 (m, 2H); 1.85 (m,
2H); 1.50-1.28 (s, 9H & m, 4H).
Example A135
4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl}-amino)-piperidine-1-carboxylic acid tert-butyl
ester
[4287] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (example A72) and commercially available
4-amino-piperidine-1-carboxylic acid tert-butyl ester the title
compound was obtained as colorless solid.
[4288] MS (ESI): m/z=540 (MH.sup.+, 100%); 484
(MH.sup.+--C.sub.4H.sub.8); 440
(MH.sup.+--C.sub.6H.sub.8O.sub.2).
[4289] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.23 (br.s, 1H, --NH);
9.02 (s, 1H); 8.43 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01 (s, 2H); 4.08 (m, 1H); 4.03
(t, J=4.7, 2H); 3.87 (m, 2H); 3.39 (t, J=4.7, 2H); 3.02 (s, 3H
& m, 2H); 1.94 (m, 2H); 1.42 (s, 9H & m, 2H).
Example A136
4-{[4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[3-
,2-d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester
[4290] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid (example A84) and commercially
available 4-amino-piperidine-1-carboxylic acid the title compound
is obtained as colorless foam.
[4291] MS (ESI): m/z=570 (MH.sup.+, 100%).
[4292] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.04 (br.s, 1H, --NH);
9.02 (s, 1H); 8.49 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.51 (d,
J=11.5, 1H); 7.02 (d, J=6.9, 1H); 5.39 (s, 2H); 4.07 (m, 1H); 3.88
(d, J=6.9, 2H); 3.87 (m, 2H); 3.47 (s, 3H); 3.03 (m, 2H); 1.93 (m,
2H); 1.46 (m, 2H); 1.42 (s, 9H); 0.95 (m, 1H); 0.35 (m, 2H); 0.21
(m, 2H).
Example A137
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester
[4293] Starting from
4-[2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid (example A85) and
commercially available 4-amino-piperidine-1-carboxylic acid the
title compound is obtained as colorless foam.
[4294] MS (ESI): m/z=576 (MH.sup.+); 520
(MH.sup.+--C.sub.4H.sub.8); 476
(MH.sup.+--C.sub.5H.sub.8O.sub.2).
[4295] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.06 (s, 1H); 8.47 (d, J=7.7, 1H, --NH); 8.33 (s, 1H); 7.64 (d,
J=10.8, 1H); 7.40 (t, J=73.1, 1H); 7.18 (d, J=6.6, 1H); 4.07 (m,
1H); 3.91 (d, J=6.9, 2H); 3.87 (m, 2H); 3.03 (m, 2H); 1.93 (m, 2H);
1.46 (m, 2H); 1.42 (s, 9H); 0.95 (m, 1H); 0.35 (m, 2H); 0.21 (m,
2H).
Example A138
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid piperidin-4-ylamide hydrochloride
[4296]
4-({1-[4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-
-d]pyrimidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid
tert-butyl ester from example A86 (4.02 g; 7.5 mmol) is dissolved
in warm (40-70.degree. C.) 2-propanol (37.5 mL). After addition of
4M HCl in dioxane (7.5 mL) the stirred reaction mixture is heated
to 80.degree. C. for two hours. Tert-butylmethylether (150 mL) is
added to the reaction mixture while still warm (40-70.degree. C.).
After cooling in an ice bath the precipitated product is collected,
washed with tert-butylmethylether and dried in high vacuo at
50.degree. C. to yield 3.35 g of the title compound as bright
yellow solid.
[4297] MS (ESI): m/z=438 (MH.sup.+, 100%).
[4298] .sup.1H-NMR (400 MHz, DMSO-d.sub.6,): 12.56 (br.s, 1H,
--NH); 9.10 (s, 1H); 9.03 (br.s, 2H, --NH.sub.2.sup.+); 8.44 (d,
J=7.3, 1H, --NH); 8.42 (2, 1H); 7.03 (d, J=8.6, 1H); 6.58 (d,
J=8.6, 1H); 6.03 (s, 2H); 4.17 (m, 1H); 3.78 (d, J=6.7, 2H); 3.32
(m, 2H); 3.07 (m, 2H); 2.13 (m, 2H); 1.83 (m, 2H); 0.88 (m, 1H);
0.30 (m, 2H); 0.12 (m, 2H).
Example A139
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4299]
Trans-[4-({1-[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-
-pyrrolo[3,2-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic
acid tert-butyl ester from example A114 (3.05 g; 5.51 mmol) is
dissolved in 2-propanol (27.5 mL). After addition of 4M HCl in
dioxane (5.5 mL) the stirred reaction mixture is heated to
80.degree. C. for two hours. Tert-butylmethylether (100 mL) is
added to the reaction mixture while still warm (40-70.degree. C.).
After cooling in an ice bath the precipitated product is collected,
washed with tert-butylmethylether and dried in high vacuo at
50.degree. C. to yield the bright yellow hydrochloric acid salt of
the title compound.
[4300] The salt is dissolved in hot (60-90.degree. C.) water (25
mL). The pH of the well stirred solution is adjusted to 9.0 by
dropwise addition of 25% NH.sub.4OH. After stirring for one hour in
an ice bath the precipitated product is collected, washed with
ice-cold water and dried in high vacuo at 50.degree. C. to yield
2.18 g of the title compound as colorless solid.
[4301] MS (ESI): m/z=454 (MH.sup.+, 100%).
[4302] .sup.1H-NMR (400 MHz, DMSO-d.sub.6, MeOH-d.sub.4): 9.00 (s,
1H); 8.39 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.50 (d, J=11.8, 1H);
6.92 (d, J=7.3, 1H); 3.97 (s, 1H); 3.94 (d, J=7.1, 2H); 3.80 (m,
1H); 2.74 (m, 1H); 2.01 (m, 2H); 1.88 (m, 2H); 1.40 (m, 2H); 1.26
(m, 2H); 0.97 (m, 1H); 0.37 (m, 2H); 0.22 (m, 2H).
[4303] The following compounds are obtained analogously to the
procedures described in above example A138 or A139.
Example A140
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-pyrimi-
dine-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4304] Starting from
trans-(4-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid
tert-butyl ester (example A87) the title compound is obtained as
colorless solid.
[4305] MS (ESI): m/z=450 (MH.sup.+, 100%).
[4306] .sup.1H-NMR (200 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.29 (d, J=8.8, 1H, --NH); 8.29 (s, 1H); 8.27 (s, 1H); 7.00
(d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 3.76 (d, J=6.7,
2H & m, 1H); 2.80 (m, 1H); 2.04 (m, 2H); 1.89 (m, 2H);
1.51-1.19 (m, 4H); 0.87 (m, 1H); 0.29 (m, 2H); 0.09 (m, 2H).
Example A141
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4307] Starting from
cis-(4-{[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester (example A88) the title compound is obtained as colorless
solid.
[4308] MS (ESI): m/z=450 (MH.sup.+, 100%).
[4309] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.33 (br.s, 1H, --NH);
9.06 (s, 1H); 8.62 (d, J=7.2, 1H, --NH); 8.30 (s, 1H); 7.89 (br.s,
2H, --NH.sub.2.sup.+); 7.02 (d, J=8.6, 1H); 6.57 (d, J=8.6, 1H);
6.00 (s, 2H); 4.11 (m, 1H); 3.77 (d, J=6.8, 2H); 3.23 (m, 1H); 1.87
(m, 4H); 1.73 (m, 4H); 0.88 (m, 1H); 0.30 (m, 2H); 0.11 (m,
2H).
Example A142
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
[4310] Starting from
(R)-3-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester (example A90) the title compound is obtained as
bright yellow solid.
Example A143
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride
[4311] Starting from
(S)-3-{[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester (example A89) the title compound is obtained as
bright yellow solid.
Example A144
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (piperidin-4-ylmethyl)-amide
[4312] Starting from
4-({[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-piperidine-1-carboxylic acid
tert-butyl ester (example A91) the title compound is obtained as
colorless solid.
Example A145
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (piperidin-3-ylmethyl)-amide
[4313] Starting from
3-({[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-piperidine-1-carboxylic acid
tert-butyl ester (example A92) the title compound is obtained as
colorless solid.
Example A146
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (pyrrolidin-3-ylmethyl)-amide
[4314] Starting from
3-({[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid
tert-butyl ester (example A93) the title compound is obtained as
colorless solid.
Example A147
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (morpholin-2-ylmethyl)-amide
[4315] Starting from
2-({[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid
tert-butyl ester (example A94) the title compound is obtained as
colorless solid.
Example A148
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (S)-piperidin-3-ylamide
[4316] Starting from
(S)-3-{[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A96) the title compound is obtained as
colorless solid.
[4317] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4318] .sup.1H-NMR (300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.03 (s,
1H); 8.51 (d, J=8.1, 1H, --NH); 8.26 (s, 1H); 7.00 (d, J=8.6, 1H);
6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 3.96 (m, 1H); 3.76 (d, J=6.7,
2H); 3.02 (m, 1H); 2.73 (m, 1H); 2.63 (m, 1H); 2.54 (m, 1H); 1.87
(m, 1H); 1.66 (m, 1H); 1.50 (m, 1H); 0.88 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example A149
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (R)-piperidin-3-ylamide
[4319] Starting from
(R)-3-{[4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A97) the title compound is obtained as
colorless solid.
[4320] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4321] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.85 (br.s, 1H, --NH);
9.38 (br.m, 2H, --NH.sub.2.sup.+); 9.13 (s, 1H); 8.60 (s, 1H); 8.51
(d, J=7.6, 1H, --NH); 7.06 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H);
6.05 (s, 2H); 4.31 (m, 1H); 3.79 (d, J=6.7, 2H); 3.38 (m, 1H); 3.18
(m, 1H); 2.97 (m, 1H); 2.91 (m, 1H); 2.04-11.71 (m, 4H); 0.90 (m,
1H); 0.31 (m, 2H); 0.14 (m, 2H).
Example A150
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4322] Starting from
trans-(4-{[4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester (example A100) the title compound is obtained as colorless
solid.
[4323] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4324] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.09 (s,
1H); 8.39 (d, J=7.9, 1H, --NH); 8.21 (s, 1H); 7.61 (d, J=8.5, 1H);
6.70 (dd, J.sup.1=8.5, J.sub.2=2.2, 1H); 6.68 (d, J=2.2, 1H); 3.92
(d, J=6.9, 2H); 3.86 (s, 3H); 3.81 (m, 1H); 3.08 (m, 1H); 2.05 (m,
4H); 1.48 (m, 4H); 0.97 (m, 1H); 0.36 (m, 2H); 0.23 (m, 2H).
Example A151
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide
[4325] Starting from
cis-(4-{[4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester
(example A99) the title compound is obtained as colorless
solid.
[4326] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4327] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.01 (s,
1H); 8.74 (d, J=7.7, 1H, --NH); 8.19 (s, 1H); 7.63 (d, J=8.5, 1H);
6.73 (dd, J.sub.1=8.5, J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 4.04
(m, 1H); 3.93 (d, J=6.9, 2H); 3.86 (s, 3H); 2.79 (m, 1H); 1.80 (m,
2H); 1.66 (m, 4H); 1.47 (m, 2H); 0.99 (m, 1H); 0.37 (m, 2H); 0.24
(m, 2H).
Example A152
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide
[4328] Starting from
4-{[4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
(example A98) the title compound is obtained as colorless
solid.
[4329] MS (ESI): m/z=422 (MH.sup.+, 100%).
[4330] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.57 (d, J=7.5, 1H, --NH); 8.25 (s, 1H); 7.63 (d, J=8.5, 1H);
6.73 (dd, J.sub.1=8.5, J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 4.18
(m, 1H); 3.93 (d, J=6.9, 2H); 3.86 (s, 3H); 3.37 (m, 2H); 3.11 (m,
2H); 2.16 (m, 2H); 1.80 (m, 2H); 0.98 (m, 1H); 0.37 (m, 2H); 0.24
(m, 2H).
Example A153
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide
[4331] Starting from
trans-(4-{[4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester (example A101) the title compound is obtained as colorless
solid.
[4332] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4333] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.04 (s,
1H); 8.41 (d, J=7.9, 1H, --NH); 8.25 (s, 1H); 7.20 (t, J=1.6, 1H);
7.12 (d, J=1.6, 2H); 3.83 (d, J=6.9, 2H & m, 1H); 3.77 (s, 3H);
3.11 (m, 1H); 2.08 (m, 2H); 2.01 (m, 2H); 1.49 (m, 4H); 0.92 (m,
1H); 0.32 (m, 2H); 0.16 (m, 2H).
Example A154
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide
[4334] Starting from
cis-(4-{[4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester
(example A102) the title compound is obtained as colorless
solid.
[4335] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4336] .sup.1H-NMR (200 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.06 (s,
1H); 8.65 (d, J=7.8, 1H, --NH); 8.23 (s, 1H); 7.19 (t, J=1.7, 1H);
7.11 (d, J=1.7, 2H); 4.04 (m, 1H); 3.83 (d, J=6.8, 2H); 3.77 (s,
3H); 2.82 (m, 1H); 1.88-1.54 (m, 6H); 1.54-1.32 (m, 2H); 0.93 (m,
1H); 0.33 (m, 2H); 0.11 (m, 2H).
Example A155
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide
[4337] Starting from
4-{[4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
(example A103) the title compound is obtained as colorless
solid.
[4338] MS (ESI): m/z=422 (MH.sup.+, 100%).
[4339] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.06 (s,
1H); 8.47 (d, J=8.0, 1H, --NH); 8.24 (s, 1H); 7.19 (t, J=1.6, 1H);
7.11 (d, J=1.6, 2H); 3.97 (m, 1H); 3.83 (d, J=6.9, 2H); 3.77 (s,
3H); 3.11 (m, 1H); 2.97 (m, 2H); 2.59 (m, 2H); 1.90 (m, 2H); 1.41
(m, 2H); 0.92 (m, 1H); 0.32 (m, 2H); 0.16 (m, 2H).
Example A156
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid (4-amino-cyclohexyl)-amide
[4340] Starting from
cis-(4-{[4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester
(example A105) the title compound is obtained as colorless
solid.
[4341] MS (ESI): m/z=424 (MH.sup.+, 100%).
[4342] .sup.1H-NMR (300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.05 (s,
1H); 8.66 (d, J=7.8, 1H; --NH); 8.26 (s, 1H); 7.86 (d, J=7.6, 1H,
--NH); 7.65 (dd, J.sub.1=8.5, J.sub.2=7.0, 1H); 7.08 (dd,
J.sub.1=12.6, J.sub.2=2.3, 1H); 6.96 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.3, 1H); 4.04 (m, 1H); 3.93 (d, J=7.0, 2H); 2.82 (m, 1H);
1.83 (s, 3H); 1.88-1.74 (m, 2H); 1.74-1.58 (m, 4H); 1.52-1.39 (m,
2H); 0.97 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example A157
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4343] Starting from
trans-(4-{[4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester (example A104) the title compound is obtained as colorless
solid.
[4344] MS (ESI): m/z=424 (MH.sup.+, 100%).
[4345] .sup.1H-NMR (300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.01 (s,
1H); 8.33 (d, J=7.9, 1H; --NH); 8.25 (s, 1H); 7.66 (dd,
J.sub.1=8.5, J.sub.2=7.0, 1H); 7.07 (dd, J.sub.1=12.6, J.sub.2=2.3,
1H); 6.95 (ddd, J.sub.1=J.sub.2=8.5, J.sub.3=2.3, 1H); 3.92 (d,
J=6.9, 2H); 3.79 (m, 1H); 2.63 (m, 1H); 1.97 (m, 2H); 1.82 (m, 2H);
1.36 (m, 2H); 1.18 (m, 2H); 0.95 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example A158
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid piperidin-4-ylamide
[4346] Starting from
4-{[4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
(example A106) the title compound is obtained as colorless
solid.
[4347] MS (ESI): m/z=410 (MH.sup.+, 100%).
[4348] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.45 (br.s, 1H, --NH);
9.11 (s, 1H); 9.10 (br.S, 2H, NH.sub.2.sup.+); 8.51 (d, J=7.7, 1H;
--NH); 8.48 (s, 1H); 7.70 (dd, J.sub.1=8.5, J.sub.2=7.0, 1H); 7.11
(dd, J.sub.1=11.6, J.sub.2=2.4, 1H); 6.99 (ddd,
J.sub.1=J.sub.2=8.5, J.sub.3=2.4, 1H); 4.17 (m, 1H); 3.94 (d,
J=7.0, 2H); 3.32 (m, 2H); 3.08 (m, 2H); 2.12 (m, 2H); 1.83 (m, 2H);
0.97 (m, 1H); 0.36 (m, 2H); 0.24 (m, 2H).
Example A159
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid piperidin-4-ylamide hydrochloride
[4349] Starting from
4-{[4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
(example A108) the title compound is obtained as bright yellow
solid.
[4350] MS (ESI): m/z=410 (MH.sup.+, 100%).
[4351] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.28 (br.s, 1H,
--NH); 9.08 (s, 1H); 8.37 (d, J=3.4, 1H); 8.34 (s, 1H, --NH); 8.09
(br.s, 3H, --NH.sub.3.sup.+); 7.47-7.36 (m, 2H); 7.20 (dd,
J.sub.1=9.1, J.sub.2=4.4, 1H); 3.90 (d, J=6.9, 2H); 3.81 (m, 1H);
3.08 (m, 1H); 2.04 (m, 4H); 1.49 (m, 4H); 0.94 (m, 1H); 0.34 (m,
2H); 0.19 (m, 2H).
Example A160
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide hydrochloride
[4352] Starting from
trans-(4-{[4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester (example A107) the title compound is obtained as bright
yellow solid.
[4353] MS (ESI): m/z=424 (MH.sup.+, 100%).
[4354] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.37 (br.s, 1H,
--NH); 9.11 (s, 1H); 9.07 (br.s, 2H, --NH.sub.2); 8.49 (d, J=7.6,
1H, --NH); 8.44 (d, J=3.3, 1H); 7.47-7.37 (m, 2H); 7.20 (dd,
J.sub.1=9.1, J.sub.2=4.4, 1H); 4.17 (m, 1H); 3.89 (d, J=6.9, 2H);
3.31 (m, 2H); 3.08 (m, 2H); 2.12 (m, 2H); 1.82 (m, 2H); 0.94 (m,
1H); 0.33 (m, 2H); 0.19 (m, 2H).
Example A161
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid (4-amino-cyclohexyl)-amide
[4355] Starting from
trans-(4-{[4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester
(example A109) the title compound is obtained as colorless
solid.
[4356] MS (ESI): m/z=406 (MH.sup.+, 100%).
[4357] .sup.1H-NMR (300 MHz, DMSO-d.sub.6, MeOH-d.sub.4): 9.02 (s,
1H); 8.34 (d, J=8.0, 1H, --NH); 8.22 (s, 1H); 7.63 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 3.91 (d, J=6.9, 2H);
3.80 (m, 1H); 2.62 (m, 1H); 1.98 (m, 2H); 1.92 (m, 2H); 1.36 (m,
2H); 1.18 (m, 2H); 0.96 (m, 1H); 0.35 (m, 2H); 0.21 (m, 2H).
Example A162
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid piperidin-4-ylamide
[4358] Starting from
4-{[4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbony-
l]-amino}-piperidine-1-carboxylic acid tert-butyl ester (example
A110) the title compound is obtained as colorless solid.
[4359] MS (ESI): m/z=392 (MH.sup.+, 100%).
[4360] .sup.1H-NMR (300 MHz, DMSO-d.sub.6, MeOH-d.sub.4): 9.06 (s,
1H); 8.48 (d, J=7.9, 1H, --NH); 8.23 (s, 1H); 7.63 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J2=0.9, 1H); 7.13 (ddd,
J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 3.98 (m, 1H); 3.91 (d,
J=6.9, 2H); 2.98 (m, 2H); 2.60 (m, 2H); 1.89 (m, 2H); 1.42 (m, 2H);
0.97 (m, 1H); 0.34 (m, 2H); 0.21 (m, 2H).
Example A163
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid piperidin-4-ylamide hydrochloride
[4361] Starting from
4-{[4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A111) the title compound is obtained as
bright yellow solid.
[4362] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4363] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.44 (br.s, 1H,
--NH); 9.13 (s, 1H & br.s, 2H, --NH.sub.2.sup.+); 8.51 (d,
J=5.6, 1H, --NH); 8.49 (s, 1H); 7.45 (d, J=9.8, 1H); 7.22 (d,
J=13.4, 1H); 4.17 (m, 1H); 3.87 (d, J=7.2, 2H & s, 3H); 3.32
(m, 2H); 3.07 (m, 2H); 2.13 (m, 2H); 1.83 (m, 2H); 0.93 (m, 1H);
0.34 (m, 2H); 0.19 (m, 2H).
Example A164
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
[4364] Starting from
(R)-3-{[4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A112) the title compound is obtained as
bright yellow solid.
[4365] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4366] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.46 (br.s, 1H, --NH);
9.29 (br.s, 1H, --NH); 9.19 (br.s, 1H, --NH); 9.11 (s, 1H); 8.55
(s, 1H); 8.53 (br.s, 1H, --NH); 7.45 (d, J=9.8, 1H); 7.22 (d,
J=13.3, 1H); 4.28 (m, 1H); 3.87 (d, J=6.7, 2H); 3.86 s, 3H); 3.38
(m, 1H); 3.20 (m, 1H); 2.97 (m, 2H); 2.04-1.71 (m, 4H); 0.94 (m,
1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example A165
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
[4367] Starting from
(R)-3-{[4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester (example A113) the title compound is obtained as
bright yellow solid.
[4368] MS (ESI): m/z=426 (MH.sup.+, 100%).
[4369] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.41 (br.s, 1H, --NH);
9.39 (br.s, 1H, --NH.sub.2); 9.11 (s, 1H); 8.69 (d, J=6.7, 1H,
--NH); 8.51 (d, J=3.3, 1H); 7.45 (d, J=9.8, 1H); 7.21 (d, J=13.3,
1H); 4.65 (m, 1H); 3.87 (d, J=6.8, 2H); 3.86 s, 3H); 3.52-3.46 (m,
1H); 3.30-3.14 (m, 1H); 2.32 (m, 1H); 2.04 (m, 1H); 0.93 (m, 1H);
0.33 (m, 2H); 0.19 (m, 2H).
solid.
Example A166
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid piperidin-4-ylamide hydrochloride
[4370] Starting from
4-{[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A115) the title compound is obtained as
bright yellow solid.
[4371] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4372] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.53 (br.s, 1H,
--NH); 9.16 (br.s, 2H, --NH.sub.2); 9.11 (s, 1H); 8.57 (d, J=3.2,
1H); 8.53 (d, J=7.6, 1H); 7.55 (d, J=11.7, 1H); 6.96 (d, J=7.3,
1H); 4.17 (m, 1H); 4.00 (s, 3H); 3.99 (d, J=5.2, 2H); 3.31 (m, 2H);
3.06 (m, 2H); 2.12 (m, 2H); 1.82 (m, 2H); 0.97 (m, 1H); 0.37 (m,
2H); 0.24 (m, 2H).
Example A167
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
[4373] Starting from
(R)-3-{[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A116) the title compound is obtained as
bright yellow solid.
[4374] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4375] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.48 (br.s, 1H, --NH);
9.28 (br.m, 2H, --NH.sub.2); 9.08 (s, 1H); 8.59 (d, J=6.8, 1H,
--NH); 8.57 (s, 1H); 7.57 (d, J=11.7, 1H); 6.96 (d, J=7.3, 1H);
4.30 (m, 1H); 4.00 (s, 3H); 3.99 (d, J=5.2, 2H); 3.39 (m, 1H); 3.20
(m, 1H); 2.99 (m, 1H); 2.97 (m, 1H); 1.98 (m, 2H); 1.76 (m, 2H);
0.98 (m, 1H); 0.38 (m, 2H); 0.25 (m, 2H).
Example A168
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (S)-piperidin-3-ylamide hydrochloride
[4376] Starting from
(S)-3-{[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A117) the title compound is obtained as
bright yellow solid.
[4377] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4378] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.48 (br.s, 1H, --NH);
9.28 (br.m, 2H, --NH.sub.2); 9.08 (s, 1H); 8.59 (d, J=6.8, 1H,
--NH); 8.57 (s, 1H); 7.57 (d, J=11.7, 1H); 6.96 (d, J=7.3, 1H);
4.30 (m, 1H); 4.00 (s, 3H); 3.99 (d, J=5.2, 2H); 3.39 (m, 1H); 3.20
(m, 1H); 2.99 (m, 1H); 2.97 (m, 1H); 1.98 (m, 2H); 1.76 (m, 2H);
0.98 (m, 1H); 0.38 (m, 2H); 0.25 (m, 2H).
Example A169
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
[4379] Starting from
(R)-3-{[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-
-d]pyrimidine-7-carbonyl]-amino}-pyrrolidine-1-carboxylic acid
tert-butyl ester (example A118) the title compound is obtained as
bright yellow solid.
[4380] MS (ESI): m/z=426 (MH.sup.+, 100%).
[4381] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.39 (br.s, 1H, --NH);
9.37 (br.s, 2H, --NH.sub.2); 9.08 (s, 1H); 8.73 (d, J=6.7, 1H;
--NH); 8.53 (d, J=3.2, 1H); 7.54 (d, J=11.8, 1H); 6.95 (d, J=7.2,
1H); 4.65 (m, 1H); 3.98 (s, 3H); 3.96 (d, J=6.2, 2H); 3.57-3.39 (m,
2H); 3.30-3.17 (m, 2H); 2.33 (m, 1H); 2.03 (m, 1H); 0.97 (m, 1H);
0.37 (m, 2H), 0.23 (m, 2H).
Example A170
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4382] Starting from
trans-(4-{[4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl
ester (example A120) the title compound is obtained as colorless
solid.
[4383] MS (ESI): m/z=420 (MH.sup.+, 100%).
[4384] .sup.1H-NMR 400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.01 (s,
1H); 8.38 (d, J=7.9, 1H, --NH); 8.21 (s, 1H); 7.45 (d, J=1.9, 1H);
7.33 (dd, J.sub.1=8.4, J.sub.2=1.9, 1H); 7.06 (d, J=8.4, 1H); 3.87
(d, J=6.8, 2H); 3.80 (m, 1H); 2.63 (m, 1H); 2.17 (s, 3H); 2.00 (m,
2H); 1.84 (m, 2H); 1.38 (m, 2H); 1.20 (m, 2H); 0.95 (m, 1H); 0.34
(m, 2H); 0.19 (m, 2H).
Example A171
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid piperidin-4-ylamide
[4385] Starting from
4-{[4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
(example A119) the title compound is obtained as colorless
solid.
[4386] MS (ESI): m/z=406 (MH.sup.+, 100%).
[4387] .sup.1H-NMR 400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.04 (s,
1H); 8.53 (d, J=7.7, 1H, --NH); 8.24 (s, 1H); 7.46 (d, J=1.9, 1H);
7.34 (dd, J.sub.1=8.4, J.sub.2=1.9, 1H); 7.07 (d, J=8.4, 1H); 4.03
(m, 1H) 3.87 (d, J=6.8, 2H); 3.13 (m, 2H); 2.80 (m, 2H); 2.34 (s,
3H); 2.01 (m, 2H); 1.57 (m, 2H); 0.95 (m, 1H); 0.34 (m, 2H); 0.20
(m, 2H).
Example A172
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid azetidin-3-ylamide
[4388] Starting from
3-{[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-azetidine-1-carboxylic acid tert-butyl
ester (example A95) the title compound is obtained as colorless
solid.
Example A173
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide
hydrochloride
[4389] Starting from
trans-[4-({1-[4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,-
2-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
tert-butyl ester (example A121) the title compound is obtained as
bright yellow solid.
[4390] MS (ESI): m/z=464 (MH.sup.+, 100%).
[4391] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.88 (br.s, 1H, --NH);
9.12 (s, 1H); 8.52 (d, J=3.1, 1H); 8.29 (d, J=7.4, 1H, --NH &
br.s, 3H, --NH.sub.3.sup.+); 7.07 (d, J=8.6, 1H); 6.62 (d, J=8.6,
1H); 6.06 (s, 2H); 3.88 (d, J=6.3, 2H); 3.82 (m, 2H); 3.07 (m, 1H);
2.41 (m, 1H); 2.06 (m, 4H); 1.70 (m, 3H); 1.63-1.40 (m, 7H).
Example A174
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid piperidin-4-ylamide hydrochloride
[4392] Starting from
4-({1-[4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid
tert-butyl ester (example A122) the title compound is obtained as
bright yellow solid.
[4393] MS (ESI): m/z=450 (MH.sup.+, 100%).
[4394] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.74 (br.s, 1H, --NH);
9.17 (br.s, 2H, --NH.sub.2.sup.+); 9.12 (s, 1H); 8.48 (d, J=3.1,
1H); 8.43 (d, J=7.5, 1H, --NH); 7.06 (d, J=8.6, 1H); 6.61 (d,
J=8.6, 1H); 6.05 (s, 2H); 4.16 (m, 1H); 3.87 (d, J=6.3, 2H); 3.31
(m, 2H); 3.07 (m, 2H); 2.40 (m, 1H); 2.12 (m, 2H); 1.83 (m, 2H);
1.70 (m, 3H); 1.52 (m, 3H).
Example A175
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid piperidin-4-ylamide
[4395] Starting from
4-{[4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (example
A123) the title compound was obtained as colorless solid.
[4396] MS (ESI): m/z=410 (MH.sup.+, 100%).
[4397] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.04 (s,
1H); 8.47 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.01 (d, J=8.6, 1H);
6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.03 (m, 1H); 3.96 (qu, J=6.9,
2H); 3.09 (m, 1H); 2.93 (m, 1H); 2.76 (m, 1H); 2.21 (m, 1H); 1.98
(m, 2H); 1.57 (m, 2H); 1.03 (t, J=6.9, 3H).
Example A176
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid (R)-pyrrolidin-3-ylamide
[4398] Starting from
(R)-3-{[4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester
(example A124) the title compound was obtained as colorless
solid.
[4399] MS (ESI): m/z=396 (MH.sup.+, 100%).
[4400] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.04 (s,
1H); 8.49 (d, J=7.3, 1H, --NH); 8.30 (s, 1H); 7.02 (d, J=8.6, 1H);
6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.45 (m, 1H); 3.96 (qu, J=6.9,
2H); 3.17 (m, 1H); 3.02 (m, 1H); 2.89 (m, 1H); 2.75 (m, 1H); 2.13
(m, 1H); 1.70 (m, 1H); 1.03 (t, J=6.9, 3H).
Example A177
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide
[4401] Starting from
4-{[4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
bonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester
(example A125) the title compound was obtained as colorless
solid.
[4402] MS (ESI): m/z=424 (MH.sup.+, 100%).
[4403] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.03 (s,
1H); 8.49 (d, J=8.0, 1H, --NH); 8.27 (s, 1H); 7.01 (d, J=8.6, 1H);
6.58 (d, J=8.6, 1H); 6.01 (s, 2H); 4.03 (m, 1H); 3.86 (t, J=6.4,
2H); 3.11 (m, 1H); 2.87 (m, 1H); 2.69 (m, 2H); 1.92 (m, 1H); 1.72
(m, 1H); 1.57 (m, 2H); 1.40 (m, 2H); 0.62 (t, J=7.4, 3H).
Example A178
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide
[4404] Starting from
(R)-3-{[4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester
(example A126) the title compound was obtained as colorless
solid.
[4405] MS (ESI): m/z=410 (MH.sup.+, 100%).
[4406] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.48 (d, J=7.3, 1H, --NH); 8.26 (s, 1H); 7.01 (d, J=8.6, 1H);
6.58 (d, J=8.6, 1H); 6.01 (s, 2H); 4.43 (m, 1H); 3.86 (t, J=6.4,
2H); 3.15 (m, 1H); 3.01 (m, 1H); 2.87 (m, 1H); 2.73 (m, 1H); 2.12
(m, 1H); 1.69 (m, 1H); 1.42 (m, 2H); 0.62 (t, J=7.4, 3H).
Example A179
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid piperidin-4-ylamide
[4407] Starting from
4-{[4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (example
A127) the title compound was obtained as colorless solid.
[4408] MS (ESI): m/z=438 (MH.sup.+, 100%).
[4409] .sup.1H-NMR 300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.03 (s,
1H); 8.50 (d, J=8.0, 1H, --NH); 8.26 (s, 1H); 7.01 (d, J=8.6, 1H);
6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.00 (m, 1H); 3.89 (t, J=6.4,
2H); 3.08 (m, 1H); 2.80 (m, 1H); 2.70-2.55 (m, 2H); 1.90 (m, 1H);
1.70 (m, 1H); 1.61-1.47 (m, 2H); 1.40 (m, 2H); 1.04 (m, 2H); 0.69
(t, J=7.4, 3H).
Example A180
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid piperidin-3-ylamide
[4410] Starting from
3-{[4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (example
A128) the title compound was obtained as colorless solid.
[4411] MS (ESI): m/z=438 (MH.sup.+, 100%).
[4412] .sup.1H-NMR (300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.03 (s,
1H); 8.46 (d, J=7.8, 0.5H, --NH); 8.42 (d, J=7.8, 0.5H, --NH); 8.27
(s, 1H); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H);
4.09-3.91 (m, 1H); 3.89 (t, J=6.4, 2H); 3.08 (m, 1H); 2.92 (m, 1H);
2.73 (m, 2H); 2.22 (m, 1H); 1.97 (m, 2H); 1.54 (m, 2H); 1.40 (m,
2H); 1.08 (m, 2H); 0.69 (t, J=7.4, 3H).
Example A181
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid (R)-pyrrolidin-3-ylamide
[4413] Starting from
(R)-3-{[4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester
(example A129) the title compound was obtained as colorless
solid.
[4414] MS (ESI): m/z=424 (MH.sup.+, 100%).
[4415] .sup.1H-NMR 300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.84 (d, J=7.3, 1H, --NH); 8.26 (s, 1H); 7.01 (d, J=8.6, 1H);
6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 4.43 (m, 1H); 3.89 (t, J=6.4,
2H); 3.14 (m, 1H); 3.01 (m, 1H); 2.89 (m, 1H); 2.74 (m, 1H); 2.12
(m, 1H); 1.69 (m, 1H); 1.40 (m, 2H); 1.07 (m, 2H); 0.69 (t, J=7.4,
3H).
Example A182
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4416] Starting from
trans-[4-({4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl
ester (example A130) the title compound was obtained as colorless
solid.
[4417] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4418] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 8.99 (s,
1H); 8.45 (d, J=7.9, 1H, --NH); 8.23 (s, 1H); 7.70 (d, J=8.3, 1H);
6.77 (s, 1H); 6.75 (dd, J.sub.1=8.3, J.sub.2=2.1, 1H); 4.25 (t,
J=4.6, 2H); 3.88 (s, 3H); 3.84 (m, 1H); 3.55 (t, J=4.6, 2H); 3.14
(s, 3H); 3.13 (m, 1H); 2.12-1.97 (m, 4H); 1.49 (m, 4H).
Example A183
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide
[4419] Starting from
cis-[4-({4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl ester
(example A131) the title compound was obtained as colorless
solid.
[4420] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4421] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.03 (s,
1H); 8.76 (d, J=7.4, 1H, --NH); 8.23 (s, 1H); 7.71 (d, J=8.3, 1H);
6.78 (s, 1H); 6.75 (dd, J.sub.1=8.3, J.sub.2=2.1, 1H); 4.25 (t,
J=4.6, 2H); 3.88 (s, 3H); 3.56 (t, J=4.6, 2H); 3.41 (m, 1H); 3.15
(s, 3H); 3.05 (m, 1H); 2.12-1.97 (m, 4H); 1.49 (m, 4H).
Example A184
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide
[4422] Starting from
4-({4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carbonyl}-amino)-piperidine-1-carboxylic acid tert-butyl ester
(example A132) the title compound was obtained as colorless
solid.
[4423] MS (ESI): m/z=426 (MH.sup.+).
[4424] .sup.1H-NMR (400 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.57 (d, J=7.7, 1H, --NH); 8.24 (s, 1H); 7.72 (d, J=8.2, 1H);
6.77 (s, 1H); 6.75 (dd, J.sub.1=8.2, J.sub.2=2.2, 1H); 4.25 (t,
J=4.6, 2H); 4.06 (m, 1H); 3.88 (s, 3H); 3.55 (t, J=4.6, 2H); 3.15
(s, 3H & m, 2H); 1.92-1.87 (m, 4H); 1.73 (m, 2H); 1.61 (m,
2H).
Example A185
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4425] Starting from
trans-[4-({4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2--
d]pyrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid
tert-butyl ester (example A133) the title compound was obtained as
colorless solid.
[4426] MS (ESI): m/z=454 (MH.sup.+, 100%).
[4427] .sup.1H-NMR (200 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.00 (s,
1H); 8.31 (d, J=7.9, 1H, --NH); 8.24 (s, 1H); 7.01 (d, J=8.6, 1H);
6.60 (d, J=8.6, 1H); 6.01 (s, 2H); 4.02 (t, J=4.7, 2H); 3.82 (m,
1H); 3.39 (t, J=4.7, 2H); 3.03 (s, 3H); 2.81 (m, 1H); 1.92-1.38 (m,
8H).
Example A186
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (4-amino-cyclohexyl)-amide
[4428] Starting from
cis-[4-({4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]-
pyrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid tert-butyl
ester (example A134) the title compound was obtained as colorless
solid.
[4429] MS (ESI): m/z=454 (MH.sup.+, 100%).
[4430] .sup.1H-NMR (200 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.64 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.01 (d, J=8.6, 1H);
6.62 (d, J=8.6, 1H); 6.01 (s, 2H); 4.02 (t, J=4.7, 2H & m, 1H);
3.40 (t, J=4.7, 2H); 3.03 (s, 3H); 2.64 (m, 1H); 2.00 (m, 2H); 1.86
(m, 2H); 1.52-1.16 (m, 4H).
Example A187
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide
[4431] Starting from
4-({4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl}-amino)-piperidine-1-carboxylic acid tert-butyl
ester (example A135) the title compound was obtained as colorless
solid.
[4432] MS (ESI): m/z=440 (MH.sup.+, 100%).
[4433] .sup.1H-NMR (200 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.02 (s,
1H); 8.40 (d, J=8.0, 1H, --NH); 8.27 (s, 1H); 7.01 (d, J=8.6, 1H);
6.61 (d, J=8.6, 1H); 6.01 (s, 2H); 4.03 (t, J=4.7, 2H); 3.96 (m,
1H); 3.39 (t, J=4.7, 2H); 3.02 (s, 3H); 2.98 (m, 2H); 2.60 (m, 2H);
1.90 (m, 2H); 1.41 (m, 2H).
Example A188
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid piperidin-4-ylamide hydrochloride
[4434] Starting from
4-{[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[-
3,2-d]pyrimidine-7-carbonyl]amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A136) the title compound is obtained as
pale yellow solid.
[4435] MS (ESI): m/z=426 (MH.sup.+, 100%).
[4436] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.66 (br.s, 1H, --NH);
10.91 (br.s, 1H, --OH); 9.19 (br.s, 2H, --NH.sub.2.sup.+); 9.12 (s,
1H); 8.64 (d, J=2.9, 1H); 8.53 (d, J=7.5, 1H, --NH); 7.53 (d,
J=11.5, 1H); 6.85 (d, J=7.3, 1H); 4.17 (m, 1H); 3.85 (d, J=6.9,
2H); 3.32 (m, 2H); 3.06 (m, 2H); 2.11 (m, 2H); 1.85 (m, 2H); 0.99
(m, 1H); 0.36 (m, 2H); 0.26 (m, 2H).
Example A189
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide
hydrochloride
[4437] Starting from
4-{[4-(2-cyclopropylmethoxy-5-fluoro-4-methoxymethoxy-phenyl)-5H-pyrrolo[-
3,2-d]pyrimidine-7-carbonyl]-amino}-piperidine-1-carboxylic acid
tert-butyl ester (example A136) the title compound is obtained as
pale yellow solid.
[4438] MS (ESI): m/z=476 (MH.sup.+, 100%).
[4439] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.47 (br.s, 1H, --NH);
9.16 (br.s, 2H, --NH.sub.2.sup.+); 9.12 (s, 1H); 8.51 (d, J=7.5,
1H, --NH); 8.50 (s, 1H); 7.67 (d, J=10.9, 1H); 7.45 (t, J=72.5,
1H); 7.21 (d, J=6.0, 1H); 4.14 (m, 1H); 3.93 (d, J=7.1, 2H); 3.31
(m, 2H); 3.07 (m, 2H); 2.13 (m, 2H); 1.83 (m, 2H); 0.96 (m, 1H);
0.35 (m, 2H); 0.23 (m, 2H).
Example A190
(S)-1-(4-Amino-piperidin-1-yl)-2-hydroxy-propan-1-one
hydrochloride
[4440] To a solution of 4-amino-piperidine-4-carboxylic acid
tert-butyl ester (2.50 g, 12.48 mmol) and Huenigs base (3.2 mL;
18.7 mmol) in dichloromethane (15 mL) is added
(S)-2-acetoxypropionyl chloride (1.9 mL; 15.0 mmol) under
ice-cooling. The mixture is stirred overnight at ambient
temperature. The solvent is evaporated and the obtained crude
product is partitioned between ethyl acetate and saturated sodium
bicarbonate solution. Drying and evaporation of the solvent gave an
orange oil (4.14 g) which is dissolved in methanol (30 mL). A 4M
HCl in 1,4-dioxane (30 mL) is added and the mixture is stirred for
20 min at ambient temperature. The volatiles are evaporated and the
obtained solid is triturated with diethyl ether. Recrystallization
from methanol/1,4-dioxane gave 1.63 g of the title compound as
white solid.
[4441] MS (ESI): m/z=173 (MH.sup.+, 100%).
[4442] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 8.20 (br.s, 3H,
--NH.sub.3.sup.+); 4.85 (br.s, 1H, --OH); 4.30 (m, 2H); 4.00 (m,
1H); 3.10 (m, 2H); 2.30 (m, 1H); 2.00 (m, 2H); 1.40 (m, 2H); 1.18
(d, 3H, J=6.0).
Example A191
1-(4-Amino-piperidin-1-yl)-ethanone
[4443] To a solution of 4-amino-piperidine-4-carboxylic acid
tert-butyl ester (2.50 g; 12.5 mmol) and Huenigs base (3.2 mL) in
dichloromethane (15 mL) is added acetyl chloride (1.1 mL; 15.0
mmol) under ice-cooling. The mixture is stirred overnight at
ambient temperature. The solvent is evaporated and the obtained
crude is partitioned between ethyl acetate and 1M aqueous HCl.
Drying and evaporation of the solvent gave an orange oil which is
dissolved in dichloromethane (38 mL). Trifluoroacetic acid (19 mL)
is added and the mixture is stirred for 20 min at ambient
temperature. The volatiles are completely evaporated at 35.degree.
C. bath temperature and the obtained residue is dissolved in a
mixture of dichloromethane/methanol (95:5 v/v). Solid sodium
carbonate is added and the suspension is stirred at ambient
temperature overnight. Filtration and evaporation of the solvent
gave 0.98 g of the title compound as slightly brown oil.
[4444] MS (ESI): m/z=142 (MH.sup.+, 100%).
[4445] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 4.12 (m, 1H); 3.65 (m,
1H); 3.35 (br.s, 2H, --NH); 3.00 (m, 1H); 2.74 (m, 1H); 2.57 (m,
1H); 1.95 (s, 3H); 1.68 (m, 2H); 0.98 (m, 2H).
[4446] The following compound is obtained analogously to the
procedure described in above example A191.
Example A192
1-(4-Amino-piperidin-1-yl)-2-methoxy-ethanone
[4447] Starting from 4-amino-piperidine-4-carboxylic acid
tert-butyl ester and methoxy-acetyl chloride the title compound is
obtained as slightly brown oil.
[4448] MS (ESI): m/z=173 (MH.sup.+, 100%).
Example A193
trans-(4-Cyclopropylcarbamoyl-cyclohexyl)-carbamic acid tert-butyl
ester
[4449] To a stirred mixture of
trans-4-tert-butoxycarbonylamino-cyclohexanecarboxylic acid (6.1 g,
25.0 mmol) and cyclopropylamine (1.9 mL, 27.5 mmol) in
dichloromethane (125 mL),
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.3 g;
27.5 mmol) is added in one portion. The reaction is stirred at
ambient temperature for 48 hours. The solvent is evaporated and the
crude is stirred in ice-cold 1N hydrochloric acid (100 mL) for 30
min. The solid product is isolated by suction filtration, washed
with small portions of water and recrystallized from ethanol/water
to deliver 5.2 g of the title compound as colorless solid.
[4450] MS (ESI): m/z=305 (MNa.sup.+); 283 (MH.sup.+); 227
(MH.sup.+--C.sub.4H.sub.8, 100%).
[4451] .sup.1H-NMR (200 MHz, DMSO-d.sub.6,): 7.70 (d, J=4.1, 1H,
--NH); 6.64 (d, J=7.6, 1H, --NH); 3.13 (m, 1H); 2.57 (m, 1H); 1.91
(m, 1H); 1.86-1.58 (m, 4H); 1.37 (m, 9H); 1.33 (m, 2H); 1.09 (m,
2H); 0.57 (m, 2H); 0.34 (m, 2H).
[4452] The following compound is obtained analogously to the
procedure described in above example A193.
Example A194
trans-[4-(2-Methoxy-ethylcarbamoyl)-cyclohexyl]-carbamic acid
tert-butyl ester
[4453] Starting from
trans-4-tert-butoxycarbonylamino-cyclohexanecarboxylic acid and
2-methoxy-ethylamine the title compound is obtained as colorless
solid.
[4454] MS (ESI): m/z=323 (MNa.sup.+); 301 (MH.sup.+, 100%); 245
(MH.sup.+--C.sub.4H.sub.8).
[4455] .sup.1H-NMR (200 MHz, DMSO-d.sub.6,): 7.72 (t, J=5.4, 1H,
--NH); 6.65 (d, J=7.7, 1H, --NH); 3.30 (t, J=5.3, 2H); 3.23 (s,
3H); 3.18 (m, 2H & m, 1H); 2.01 (m, 1H); 1.73 (m, 4H); 1.37 (m,
9H); 1.34 (m, 2H); 1.11 (m, 2H).
Example A195
trans-4-Amino-cyclohexanecarboxylic acid cyclopropylamide
hydrochloride
[4456] Trans-(4-Cyclopropylcarbamoyl-cyclohexyl)-carbamic acid
tert-butyl ester from example A193 (5.0 g; 17.7 mmol) is suspended
in 1,4-dioxane (72 mL). 4N hydrochloric acid in 1,4-dioxane (18.0
mL) is added and the mixture is stirred at 80.degree. C. for six
hours. The product is precipitated with tert-butylmethylether at
ice bath temperature, isolated by suction filtration, washed with
small portions of tert-butylmethylether and dried under reduced
pressure to deliver 3.8 g of the title compound as colorless
solid.
[4457] MS (ESI): m/z=183 (MH.sup.+, 100%); 166
MH.sup.+--NH.sub.3).
[4458] .sup.1H-NMR (200 MHz, DMSO-d.sub.6,): 8.07 (br.s, 1H,
--NH.sub.3.sup.+); 7.84 (d, J=4.0, 1H, --NH); 2.93 (m, 1H); 2.59
(m, 1H); 1.97 (m, 3H); 1.73 (m, 2H); 1.34 (m, 4H); 0.58 (m, 2H);
0.35 (m, 2H).
[4459] The following compound is obtained analogously to the
procedure described in above example A195.
Example A196
trans-4-Amino-cyclohexanecarboxylic acid (2-methoxy-ethyl)-amide
hydrochloride
[4460] Starting from
trans-[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-carbamic acid
tert-butyl ester (example A194) the title compound is obtained as
colorless solid.
[4461] MS (ESI): m/z=201 (MH.sup.+, 100%); 183
MH.sup.+--NH.sub.3).
[4462] .sup.1H-NMR (200 MHz, DMSO-d.sub.6,): 8.19 (br.s, 1H,
--NH.sub.3.sup.+); 7.87 (br.s, 1H, --NH); 3.31 (t, J=5.4, 2H); 3.23
(s, 3H); 3.16 (t, J=5.4, 2H); 2.91 (m, 1H); 2.08 (m, 1H); 1.99 (m,
2H); 1.76 (m, 2H); 1.38 (m, 2H).
Example 1
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (1-propionyl-piperidin-4-yl)-amid
[4463]
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid piperidin-4-ylamide hydrochloride from
example A138 (472 mg; 1.0 mmol) and DBU (2.5 mmol) is dissolved in
dry dichloromethane (5 mL). Propionyl chloride (1.1 mmol) is
syringed into the reaction mixture at ice bath temperature. After
complete addition stirring is continued at ambient temperature over
night. Methanol (1 mL) is added and stirring is continued for two
hours. The volatiles are evaporated. The residue is purified by
reversed phase preparative HPLC. The collected product fraction is
freeze-dried to yield 375 mg of the title compound as colorless
solid.
[4464] MS (ESI): m/z=492.1 (MH.sup.+).
[4465] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.02 (s, 1H); 8.45 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.00 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.23 (m, 1H); 4.14
(m, 1H); 3.83 (m, 1H); 3.76 (d, J=6.8, 2H); 3.24 (m, 1H); 2.92 (m,
1H); 2.35 (qu, J=7.4, 2H); 1.97 (m, 2H); 1.53 (m, 1H); 1.40 (m,
1H); 1.01 (t, J=7.4, 3H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m,
2H).
[4466] The following compounds are obtained analogously to the
procedure described in above example 1.
Example 2
4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester
[4467] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A138)
and ethyl chloroformate the title compound is obtained as colorless
solid.
[4468] MS (ESI): m/z=494 (MH.sup.+).
[4469] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.44 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.08 (m, 1H &
qu, J=7.1, 2H); 3.91 (m, 2H); 3.76 (d, J=6.8, 2H); 3.08 (m, 2H);
1.95 (m, 2H); 1.47 (m, 2H); 1.20 (t, J=7.1, 3H); 0.87 (m, 1H); 0.29
(m, 2H); 0.10 (m, 2H).
Example 3
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4470] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A138)
and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4471] MS (ESI): m/z=508 (MH.sup.+).
[4472] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.03 (s, 1H); 8.45 (d, J=7.8, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.15 (m, 2H); 4.12
(s, 2H); 3.76 (m, 1H & d, J=6.8, 2H); 3.31 (s, 3H); 3.21 (m,
1H); 2.94 (m, 1H); 1.97 (m, 2H); 1.55 (m, 1H); 1.42 (m, 1H); 0.87
(m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 4
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4473] Starting from
trans-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and acetyl chloride the title compound is obtained as colorless
solid.
[4474] MS (ESI): m/z=492 (MH.sup.+).
[4475] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.42 (br. S, 1H,
--NH); 9.03 (s, 1H); 8.30 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.74
(d, J=7.7, 1H, --NH); 7.00 (d, J=8.5, 1H); 6.56 (d, J=8.5, 1H);
6.00 (s, 2H); 3.82 (m, 1H); 3.76 (d, J=6.7, 2H); 3.58 (m, 1H); 2.01
(.about.d; J .about.10.0, 2H); 1.86 (.about.d, J .about.10.2, 2H);
1.63 (s, 3H); 1.42 (m, 2H); 1.31 (m, 2H), 0.87 (m, 1H); 0.29 (m,
2H); 0.11 (m, 2H).
Example 5
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide
[4476] Starting from
trans-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4477] MS (ESI): m/z=518 (MH.sup.+).
[4478] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.23 (br. S, 1H,
--NH); 9.03 (s, 1H); 8.31 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.96
(d, J=7.7, 1H, --NH); 7.00 (d, J=8.5, 1H); 6.56 (d, J=8.5, 1H);
6.00 (s, 2H); 3.82 (m, 1H); 3.76 (d, J=6.8, 2H); 3.61 (m, 1H); 2.02
(.about.d; J .about.10.0, 2H); 1.87 (.about.d, J .about.10.2, 2H);
1.54 (m, 1H); 1.38 (m, 4H); 0.87 (m, 1H); 0.64 (m, 4H); 0.31 (m,
2H); 0.11 (m, 2H).
Example 6
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,-
2-d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid
ethyl ester
[4479] Starting from
trans-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and ethyl chloroformate the title compound is obtained as colorless
solid.
[4480] MS (ESI): m/z=522 (MH.sup.+).
[4481] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.25 (br. s, 1H,
--NH); 9.03 (s, 1H); 8.29 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.02
(d, J=9.2, 1H, --NH); 7.00 (d, J=8.5, 1H); 6.56 (d, J=8.5, 1H);
6.00 (s, 2H); 3.98 (qu, J=7.0, 2H); 3.79 (m, 1H); 3.76 (d, J=6.7,
2H); 3.31 (m, 1H); 2.00 (.about.d, J .about.10.3, 2H); 1.87
(.about.d, J .about.11.4, 2H); 1.37 (m, 4H); 1.16 (t, J=7.0, 3H);
0.86 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 7
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4482] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and acetyl chloride the title compound is obtained as colorless
solid.
[4483] MS (ESI): m/z=492 (MH.sup.+).
[4484] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.24 (br.s, 1H, --NH);
9.06 (s, 1H); 8.56 (d, J=7.6, 1H, --NH); 8.28 (s, 1H); 7.86 (d,
J=7.4, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01
(s, 2H); 4.03 (m, 1H); 3.77 (m, 1H & d, J=6.7, 2H); 1.84 (s,
3H); 1.73 (m, 6H); 1.59 (m, 2H); 0.88 (m, 1H); 0.30 (m, 2H); 0.11
(m, 2H).
Example 8
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
{4-[(1-cyclopropyl-methanoyl)-amino]-cyclohexyl}-amide
[4485] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4486] MS (ESI): m/z=518 (MH.sup.+).
[4487] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.24 (br.s, 1H, --NH);
9.07 (s, 1H); 8.58 (d, J=7.5, 1H, --NH); 8.29 (s, 1H); 8.07 (d,
J=7.4, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01
(s, 2H); 4.03 (m, 1H); 3.77 (m, 1H & d, J=6.7, 2H); 1.79 (m,
1H); 1.67 (m, 8H); 0.87 (m, 1H); 0.65 (m, 4H); 0.31 (m, 2H); 0.11
(m, 2H).
Example 9
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide
[4488] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4489] MS (ESI): m/z=522 (MH.sup.+).
[4490] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.22 (br.s, 1H, --NH);
9.06 (s, 1H); 8.59 (d, J=7.4, 1H, --NH); 8.28 (s, 1H); 7.70 (d,
J=7.7, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01
(s, 2H); 4.06 (m, 1H); 3.82 (s, 2H); 3.77 (m, 1H & d, J=6.8,
2H); 3.31 (s, 3H); 1.80 (m, 3H); 1.74 (m, 2H); 1.69 (m, 4H); 0.86
(m, 1H); 0.30 (m, 2H); 0.11 (m, 2H).
Example 10
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidin-7-yl]-methanoyl}-amino)-cyclohexyl]-carbamic acid ethyl
ester
[4491] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and ethyl chloroformate the title compound is obtained as colorless
solid.
[4492] MS (ESI): m/z=522 (MH.sup.+).
[4493] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.26 (br.s, 1H, --NH);
9.05 (s, 1H); 8.60 (d, J=7.7, 1H, --NH); 8.27 (s, 1H); 7.23 (d,
J=7.7, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01
(s, 2H); 3.99 (m, 1H & qu, J=7.1, 2H); 3.50 (m, 1H); 1.80 (m,
3H); 1.78 (m, 2H); 1.67 (m, 6H); 1.17 (t, J=7.1, 3H); 0.88 (m, 1H);
0.30 (m, 2H); 0.11 (m, 2H).
Example 11
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4494] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A138)
and acetyl chloride the title compound is obtained as colorless
solid.
[4495] MS (ESI): m/z=478 (MH.sup.+).
[4496] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
9.03 (s, 1H); 8.45 (d, J=7.8, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.21 (m, 1H); 4.13
(m, 1H); 3.81 (m, 1H); 3.76 (d, J=6.8, 2H); 3.24 (m, 1H); 2.91 (m,
1H); 2.04 (s, 3H); 1.97 (m, 2H); 1.56 (m, 1H); 1.40 (m, 1H); 0.87
(m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 12
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]amide
[4497] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A138)
and cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4498] MS (ESI): m/z=504 (MH.sup.+).
[4499] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.03 (s, 1H); 8.46 (d, J=7.8, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.18 (m, 3H); 3.76
(d, J=6.8, 2H); 3.31 (m, 1H); 2.96 (m, 1H); 2.01 (m, 3H); 1.54 (m,
1H); 1.42 (m, 1H); 0.87 (m, 1H); 0.72 (m, 4H); 0.29 (m, 2H); 0.13
(m, 2H).
Example 13
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)pyrrolidin-3-yl]-amide
[4500] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4501] MS (ESI): m/z=494 (MH.sup.+).
[4502] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 0.5H); 9.01 (s, 0.5H); 8.57 (d, J=6.7, 0.5H, --NH); 8.55
(d, J=6.0, 0.5H, --NH); 8.31 (s, 1H); 7.00 (d, J=8.6, 1H); 6.56 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 4.06 (d,
J=4.0, 1H); 4.01 (d, J=1.5, 1H); 3.82-3.67 (m, 1H); 3.76 (d, J=6.7,
2H); 3.61-3.45 (m, 2H); 3.38 (m, 1H); 3.32 (s, 1.5H); 3.30 (s,
1.5H); 2.31-2.17 (m, 1H); 2.06 (m, 0.5H); 1.93 (m, 0.5H); 0.87 (m,
1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 14
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((R)-1-formyl-pyrrolidin-3-yl)-amide
[4503] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and acetic formic anhydride the title compound is obtained as
colorless solid.
[4504] MS (ESI): m/z=450 (MH.sup.+).
[4505] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 0.5H); 9.02 (s, 0.5H); 8.57 (d, J=6.9, 0.5H, --NH); 8.53
(d, J=6.9, 0.5H, --NH); 8.32 (s, 1H); 8.22 (s, 1H); 7.01 (d, J=8.6,
1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.56 (m, 1H); 3.85 (m,
0.5H); 3.76 (d, J=6.8, 2H); 3.66 (m, 1H & 0.5H); 3.47 (m, 1H
& 0.5H); 3.27 (m, 0.5H); 2.26 (m, 1H); 2.01 (m, 1H); 0.87 (m,
1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 15
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide
[4506] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and acetyl chloride the title compound is obtained as
colorless solid.
[4507] MS (ESI): m/z=464 (MH.sup.+).
[4508] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 1H); 8.58 (d, J=6.9, 0.5H, --NH); 8.55 (d, J=6.9, 0.5H,
--NH); 8.31 (d, J=1.6, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6,
1H); 6.00 (s, 2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 3.84 (m, 0.5H);
3.76 (d, J=6.7, 2H); 3.64 (m, 1H & 0.5H); 3.46 (m, 1H &
0.5H); 3.31 (m, 0.5H); 2.25 (m, 1H); 2.06 (m, 0.5H); 1.98 (s,
1.5H); 1.96 (s, 1.5H); 1.95 (m, 0.5H); 0.87 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example 16
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(R)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]amide
[4509] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and cyclopropanecarbonyl chloride the title compound is
obtained as colorless solid.
[4510] MS (ESI): m/z=490 (MH.sup.+).
[4511] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 1H); 8.61 (d, J=6.9, 0.5H, --NH); 8.55 (d, J=6.9, 0.5H,
--NH); 8.32 (d, J=2.6, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6,
1H); 6.00 (s, 2H); 4.65 (m, 0.5H); 4.54 (m, 0.5H); 4.02 (m, 0.5H);
3.82 (m, 1H); 3.76 (d, J=6.7, 2H); 3.65 (m, 1H); 3.51 (m, 1H); 3.35
(m, 0.5H); 2.33 (m, 0.5H); 2.21 (m, 0.5H); 2.10 (m, 0.5H); 1.98 (m,
0.5H); 1.79 (m, 1H); 0.87 (m, 1H); 0.73 (m, 4H); 0.29 (m, 2H); 0.11
(m, 2H).
Example 17
(R)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d-
]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester
[4512] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and ethyl chloroformate the title compound is obtained as
colorless solid.
[4513] MS (ESI): m/z=494.1 (MH.sup.+).
[4514] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 1H); 8.56 (d, J=6.8, 1H, --NH); 8.31 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.52 (m, 1H); 4.05
(qu, J=7.0, 2H); 3.76 (d, J=6.7, 2H); 3.65 (m, 1H); 3.48 (m, 2H);
3.29 (m, 1H); 2.22 (m, 1H); 1.99 (m, 1H); 1.79 (m, 1H); 1.19 (t,
J=7.0, 3H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 18
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((S)-1-formyl-pyrrolidin-3-yl)-amide
[4515] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and acetic formic anhydride the title compound is obtained as
colorless solid.
[4516] MS (ESI): m/z=450 (MH.sup.+).
[4517] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 0.5H); 9.02 (s, 0.5H); 8.57 (d, J=6.9, 0.5H, --NH); 8.53
(d, J=6.9, 0.5H, --NH); 8.32 (s, 1H); 8.22 (s, 1H); 7.01 (d, J=8.6,
1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.56 (m, 1H); 3.85 (m,
0.5H); 3.76 (d, J=6.8, 2H); 3.66 (m, 1H & 0.5H); 3.47 (m, 1H
& 0.5H); 3.27 (m, 0.5H); 2.26 (m, 1H); 2.01 (m, 1H); 0.87 (m,
1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 19
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((S)-1-acetyl-pyrrolidin-3-yl)-amide
[4518] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and acetyl chloride the title compound is obtained as
colorless solid.
[4519] MS (ESI): m/z=464 (MH.sup.+).
[4520] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 1H); 8.58 (d, J=6.9, 0.5H, --NH); 8.55 (d, J=6.9, 0.5H,
--NH); 8.31 (d, J=1.6, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6,
1H); 6.00 (s, 2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 3.84 (m, 0.5H);
3.76 (d, J=6.7, 2H); 3.64 (m, 1H & 0.5H); 3.46 (m, 1H &
0.5H); 3.31 (m, 0.5H); 2.25 (m, 1H); 2.06 (m, 0.5H); 1.98 (s,
1.5H); 1.96 (s, 1.5H); 1.95 (m, 0.5H); 0.87 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example 20
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(S)-1-(1-cyclopropyl-methanoyl)-pyrrolidin-3-yl]amide
[4521] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and cyclopropanecarbonyl chloride the title compound is
obtained as colorless solid.
[4522] MS (ESI): m/z=490 (MH.sup.+).
[4523] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 1H); 8.61 (d, J=6.9, 0.5H, --NH); 8.55 (d, J=6.9, 0.5H,
--NH); 8.32 (d, J=2.6, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6,
1H); 6.00 (s, 2H); 4.65 (m, 0.5H); 4.54 (m, 0.5H); 4.02 (m, 0.5H);
3.82 (m, 1H); 3.76 (d, J=6.7, 2H); 3.65 (m, 1H); 3.51 (m, 1H); 3.35
(m, 0.5H); 2.33 (m, 0.5H); 2.21 (m, 0.5H); 2.10 (m, 0.5H); 1.98 (m,
0.5H); 1.79 (m, 1H); 0.87 (m, 1H); 0.73 (m, 4H); 0.29 (m, 2H); 0.11
(m, 2H).
Example 21
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-pyrrolidin-3-yl]amide
[4524] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4525] MS (ESI): m/z=494 (MH.sup.+).
[4526] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 0.5H); 9.01 (s, 0.5H); 8.57 (d, J=6.7, 0.5H, --NH); 8.55
(d, J=6.0, 0.5H, --NH); 8.31 (s, 1H); 7.00 (d, J=8.6, 1H); 6.56 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 4.06 (d,
J=4.0, 1H); 4.01 (d, J=1.5, 1H); 3.82-3.67 (m, 1H); 3.76 (d, J=6.7,
2H); 3.61-3.45 (m, 2H); 3.38 (m, 1H); 3.32 (s, 1.5H); 3.30 (s,
1.5H); 2.31-2.17 (m, 1H); 2.06 (m, 0.5H); 1.93 (m, 0.5H); 0.87 (m,
1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 22
(S)-3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d-
]pyrimidin-7-yl]-methanoyl}-amino)-pyrrolidine-1-carboxylic acid
ethyl ester
[4527] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and ethyl chloroformate the title compound is obtained as
colorless solid.
[4528] MS (ESI): m/z=494.1 (MH.sup.+).
[4529] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 1H); 8.56 (d, J=6.8, 1H, --NH); 8.31 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.52 (m, 1H); 4.05
(qu, J=7.0, 2H); 3.76 (d, J=6.7, 2H); 3.65 (m, 1H); 3.48 (m, 2H);
3.29 (m, 1H); 2.22 (m, 1H); 1.99 (m, 1H); 1.79 (m, 1H); 1.19 (t,
J=7.0, 3H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 23
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-formyl-piperidin-4-ylmethyl)-amide
[4530] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
acetic formic anhydride the title compound is obtained as colorless
solid.
[4531] MS (ESI): m/z=478 (MH.sup.+).
[4532] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.04 (s, 1H); 8.51 (t, J=5.9, 1H, --NH); 8.28 (s, 1H); 7.97 (s,
1H); 7.01 (d, J=8.5, 1H); 6.57 (d, J=8.5, 1H); 6.00 (s, 2H); 4.18
(m, 1H); 3.77 (d, J=6.7, 2H); 3.69 (m, 1H); 3.35 (dd,
J.sub.1=J.sub.2=6.2, 2H); 3.02 (m, 1H); 2.60 (m, 1H); 1.87 (m, 1H);
1.77 (m, 2H); 1.15 (m, 1H); 1.06 (m, 1H); 0.88 (m, 1H); 0.30 (m,
2H); 0.11 (m, 2H).
Example 24
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-piperidin-4-ylmethyl)-amide
[4533] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
acetyl chloride the title compound is obtained as colorless
solid.
[4534] MS (ESI): m/z=492 (MH.sup.+).
[4535] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.50 (t, J=6.1, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.38 (m, 1H); 3.82
(m, 1H); 3.77 (d, J=6.8, 2H); 3.35 (dd, J.sub.1=J.sub.2=6.0, 2H);
3.01 (m, 1H); 2.50 (m, 1H); 1.98 (s, 3H); 1.82 (m, 1H); 1.74 (m,
2H); 1.20 (m, 1H); 1.06 (m, 1H); 0.88 (m, 1H); 0.30 (m, 2H); 0.11
(m, 2H).
Example 25
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-ylmethyl]-amide
[4536] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4537] MS (ESI): m/z=518 (MH.sup.+).
[4538] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.51 (t, J=6.1, 1H, --NH); 8.27 (d, J=2.2, 1H); 7.01
(d, J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.36 (m, 1H);
4.28 (m, 1H); 3.77 (d, J=6.7, 2H); 3.35 (dd, J.sub.1=J.sub.2=6.2,
2H); 3.08 (m, 1H); 2.58 (m, 1H); 1.97 (m, 1H); 1.86 (m, 2H); 1.74
(m, 1H); 1.20 (m, 1H); 1.09 (m, 1H); 0.88 (m, 1H); 0.68 (m, 4H);
0.30 (m, 2H); 0.10 (m, 2H).
Example 26
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-ylmethyl]-amide
[4539] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4540] MS (ESI): m/z=522 (MH.sup.+).
[4541] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.26 (br.s, 1H, --NH);
9.03 (s, 1H); 8.50 (t, J=6.1, 1H, --NH); 8.27 (d, J=2.3, 1H); 7.01
(d, J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.35 (m, 1H);
4.09 (d, J=13.6, 1H); 4.02 (d, J=13.6, 1H); 3.80 (m, 1H); 3.77 (d,
J=6.7, 2H); 3.34 (dd, J.sub.1=J.sub.2=6.2, 2H); 3.27 (s, 3H); 2.96
(m, 1H); 2.57 (m, 1H); 1.84 (m, 1H); 1.75 (m, 2H); 1.20 (m, 1H);
1.09 (m, 1H); 0.87 (m, 1H); 0.30 (m, 2H); 0.10 (m, 2H).
Example 27
4-[({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]py-
rimidin-7-yl]-methanoyl}-amino)-methyl]-piperidine-1-carboxylic
acid ethyl ester
[4542] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4543] MS (ESI): m/z=522 (MH.sup.+).
[4544] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.50 (t, J=6.0, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.03 (qu, J=7.1,
2H); 3.98 (m, 2H); 3.77 (d, J=6.7, 2H); 3.34 (dd,
J.sub.1=J.sub.2=6.2, 2H); 2.77 (m, 2H); 1.77 (m, 1H); 1.73 (m, 2H);
1.17 (t, J=7.1, 3H); 1.10 (m, 2H); 0.88 (m, 1H); 0.30 (m, 2H); 0.10
(m, 2H).
Example 28
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-formyl-piperidin-3-ylmethyl)-amide
[4545] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and
acetic formic anhydride the title compound is obtained as colorless
solid.
[4546] MS (ESI): m/z=478 (MH.sup.+).
[4547] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.05 (s, 0.5H); 9.04 (s, 0.5H); 8.52 (br.s, 1H, --NH); 8.29 (s,
0.5H); 8.28 (s, 0.5H); 7.98 (s, 0.5H); 7.97 (s, 0.5H); 7.00 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.13 (m, 0.5H); 3.90
(m, 0.5H); 3.77 (d, J=6.7, 2H); 3.64 (m, 0.5H); 3.56 (m, 0.5H);
3.36 (m, 2H); 3.02 (m, 0.5H); 2.92 (m, 0.5H); 2.78 (m, 0.5H); 2.54
(m, 0.5H); 1.87 (m, 1H); 1.71 (m, 2H); 1.33 (m, 2H); 0.89 (m, 1H);
0.30 (m, 2H); 0.11 (m, 2H).
Example 29
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-propionyl-piperidin-3-ylmethyl)-amide
[4548] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and
propionyl chloride the title compound is obtained as colorless
solid.
[4549] MS (ESI): m/z=506 (MH.sup.+).
[4550] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.03 (s, 1H); 8.51 (t, J=6.9, 1H, --NH); 8.29 (s, 0.5H); 8.28 (s,
0.5H); 7.00 (d, J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.34
(m, 0.5H); 4.13 (m, 0.5H); 3.84 (m, 0.5H); 3.77 (d, J=6.8, 2H);
3.74 (m, 0.5H); 3.34 (m, 2H); 2.99 (m, 0.5H); 2.92 (m, 0.5H); 2.71
(m, 0.5H); 2.47 (m, 0.5H); 2.30 (qu, J=7.3, 2H); 1.86 (m, 1H); 1.70
(m, 2H); 1.33 (m, 2H); 0.96 (t, J=7.3, 3H); 0.89 (m, 1H); 0.29 (m,
2H); 0.10 (m, 2H).
Example 30
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(2-methoxy-acetyl)piperidin-3-ylmethyl]-amide
[4551] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4552] MS (ESI): m/z=522 (MH.sup.+).
[4553] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.51 (br.s, 1H, --NH); 8.28 (s, 1H); 7.00 (d, J=8.6,
1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.28 (m, 0.5H); 4.02 (m,
2H); 3.77 (d, J=6.8, 2H); 3.65 (m, 0.5H); 3.34 (m, 3H); 3.27 (m,
1.5H); 3.17 (m, 1.5H); 2.97 (m, 0.5H); 2.87 (m, 0.5H); 2.74 (m,
0.5H); 2.50 (m, 0.5H); 1.83 (m, 1.5H); 1.68 (m, 1.5H); 1.33 (m,
2H); 0.89 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 31
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-piperidine-1-carboxylic acid ethyl
ester
[4554] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4555] MS (ESI): m/z=522 (MH.sup.+).
[4556] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.03 (s, 1H); 8.50 (t, J=6.1, 1H, --NH); 8.28 (s, 1H); 7.00 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.00 (qu, J=7.1,
2H); 3.97 (m, 1H); 3.83 (m, 1H); 3.77 (d, J=6.9, 2H); 2.86 (m, 1H);
2.68 (m, 1H); 1.81 (m, 1H); 1.67 (m, 2H); 1.30 (m, 2H); 1.12 (br.s,
3H); 0.88 (m, 1H); 0.29 (m, 2H); 0.11 (m, 2H).
Example 32
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-formyl-pyrrolidin-3-ylmethyl)-amide
[4557] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (pyrrolidin-3-ylmethyl)-amide (example A146)
and ethyl chloroformate the title compound is obtained as colorless
solid.
[4558] MS (ESI): m/z=464 (MH.sup.+).
[4559] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.55 (br.s, 1H, --NH); 8.29 (s, 1H); 8.16 (s, 0.5H);
8.15 (s, 0.5H); 7.01 (d, J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s,
2H); 3.77 (d, J=6.7, 2H); 3.65 (m, 1H); 3.46 (m, 3H); 3.39 (m,
0.5H); 3.26 (m, 1H); 3.07 (m, 0.5H); 2.51 (m, 1H); 2.00 (m, 1H);
1.70 (m, 1H); 0.88 (m, 1H); 0.30 (m, 2H); 0.10 (m, 2H).
Example 33
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(2-methoxy-acetyl)-pyrrolidin-3-ylmethyl]-amide
[4560] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (pyrrolidin-3-ylmethyl)-amide (example A146)
and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4561] MS (ESI): m/z=508 (MH.sup.+).
[4562] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.55 (m, 1H, --NH); 8.29 (s, 1H); 7.00 (d, J=8.6,
1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 3.99 (s, 1H); 3.98 (s, 1H);
3.77 (d, J=6.7, 2H); 3.50 (m, 4H); 3.37 (m, 0.5H); 3.29 (m, 0.5H);
3.28 (s, 1.5H); 3.27 (s, 1.5H); 3.21 (m, 0.5H); 3.13 (m, 0.5H);
2.56 (m, 0.5H); 2.44 (m, 0.5H); 2.05 (m, 0.5H); 1.95 (m, 0.5H);
1.75 (m, 0.5H); 1.65 (m, 0.5H); 0.88 (m, 1H); 0.30 (m, 2H); 0.10
(m, 2H).
Example 34
3-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid
ethyl ester
[4563] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (pyrrolidin-3-ylmethyl)-amide (example A146)
and ethyl chloroformate the title compound is obtained as colorless
solid.
[4564] MS (ESI): m/z=508 (MH.sup.+).
[4565] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.54 (t, J=6.0, 1H, --NH); 8.29 (s, 1H); 7.00 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.01 (qu, J=7.1,
2H); 3.77 (d, J=6.7, 2H); 3.46 (m, 4H); 3.29 (m, 1H); 3.09 (s, 1H);
2.50 (m, 1H); 1.99 (m, 1H); 1.69 (m, 1H); 0.88 (m, 1H); 0.30 (m,
2H); 0.10 (m, 2H).
Example 35
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-formyl-morpholin-2-ylmethyl)-amide
[4566] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (morpholin-2-ylmethyl)-amide (example A147) and
acetic formic anhydride the title compound is obtained as colorless
solid.
[4567] MS (ESI): m/z=480 (MH.sup.+).
[4568] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.30 (br.s, 1H, --NH);
9.04 (s, 0.5H); 9.03 (s, 0.5H); 8.59 (br.s, 1H, --NH); 8.30 (s,
1H); 8.05 (s, 0.5H); 8.04 (s, 0.5H); 7.01 (d, J=8.6, 1H); 6.56 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.13 (m, 0.5H); 3.98 (m, 0.5H); 3.94 (m,
1H); 3.77 (d, J=6.7, 2H); 3.72 (m, 0.5H); 3.61 (m, 1.5H); 3.50 (m,
2H); 3.39 (m, 0.5H); 3.18 (m, 0.5H); 3.00 (m, 0.5H); 2.80 (m,
0.5H); 2.62 (m, 0.5H); 0.88 (m, 1H); 0.30 (m, 2H); 0.10 (m,
2H).
Example 36
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-propionyl-morpholin-2-ylmethyl)-amide
[4569] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (morpholin-2-ylmethyl)-amide (example A147) and
propionyl chloride the title compound is obtained as colorless
solid.
[4570] MS (ESI): m/z=508 (MH.sup.+).
[4571] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.04 (s, 1H); 8.58 (br.s, 1H, --NH); 8.30 (s, 1H); 7.01 (d, J=8.6,
1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.32 (m, 0.5H); 4.16 (m,
0.5H); 3.89 (m, 1.5H); 3.76 (d, J=6.7, 2H); 3.70 (m, 0.5H); 3.63
(m, 0.5H); 3.57 (m, 1H); 3.49 (m, 2H); 3.40 (m, 0.5H); 3.13 (m,
0.5H); 2.97 (m, 0.5H); 2.66 (m, 0.5H); 2.50 (m, 0.5H); 2.35 (m,
1H); 2.28 (m, 1H); 0.98 (t, J=7.4, 3H); 0.88 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example 37
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(2-methoxy-acetyl)morpholin-2-ylmethyl]-amide
[4572] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (morpholin-2-ylmethyl)-amide (example A147) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4573] MS (ESI): m/z=524 (MH.sup.+).
[4574] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.04 (s, 1H); 8.58 (t, J=5.6, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.27 (m, 0.5H); 4.11
(m, 1.5H); 4.05 (m, 1H), 3.91 (m, 1H); 3.76 (d, J=6.7, 2H & m,
1H); 3.61 (m, 2H); 3.48 (m, 2H); 3.27 (s, 1.5H); 3.25 (s, 1.5H);
3.12 (m, 0.5H); 2.97 (m, 0.5H); 2.76 (m, 0.5H); 2.56 (m, 0.5H);
0.88 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 38
2-({[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-methyl)-morpholine-4-carboxylic acid ethyl
ester
[4575] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (morpholin-2-ylmethyl)-amide (example A147) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4576] MS (ESI): m/z=524 (MH.sup.+).
[4577] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.30 (br.s, 1H, --NH);
9.04 (s, 1H); 8.57 (t, J=6.1, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.05 (qu, J=7.1,
2H); 3.90 (m, 2H); 3.76 (d, J=6.7, 2H &m, 1H); 3.58 (m, 2H);
3.46 (m, 2H); 2.93 (m, 1H); 2.75 (m, 1H); 1.17 (t, J=7.1, 3H); 0.88
(m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 39
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-azetidin-3-yl)-amide
[4578] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid azetidin-3-ylamide (example A172) and acetyl
chloride the title compound is obtained as colorless solid.
[4579] MS (ESI): m/z=450 (MH.sup.+).
[4580] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.33 (br.s, 1H, --NH);
9.06 (s, 1H); 8.84 (d, J=7.2, 1H, --NH); 8.32 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.01 (s, 2H); 4.78 (m, 1H); 4.47
(m, 1H); 4.20 (m, 1H); 4.16 (m, 1H); 3.85 (m, 1H); 3.76 (d, J=6.7,
2H); 1.80 (s, 3H); 0.86 (m, 1H); 0.29 (m, 2H); 0.09 (m, 2H).
Example 40
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-propionyl-azetidin-3-yl)-amide
[4581] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid azetidin-3-ylamide (example A172) and propionyl
chloride the title compound is obtained as colorless solid.
[4582] MS (ESI): m/z=463 (MH.sup.+).
[4583] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --NH);
9.06 (s, 1H); 8.84 (d, J=7.2, 1H, --NH); 8.32 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.01 (s, 2H); 4.79 (m, 1H); 4.46
(m, 1H); 4.21 (m, 1H); 4.14 (m, 1H); 3.86 (m, 1H); 3.76 (d, J=6.8,
2H); 2.10 (qu, J=7.5, 2H); 0.98 (t, J=7.5, 3H); 0.86 (m, 1H); 0.29
(m, 2H); 0.09 (m, 2H).
Example 41
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-methoxy-ethanoyl)-azetidin-3-yl]amide
[4584] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid azetidin-3-ylamide (example A172) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4585] MS (ESI): m/z=479 (MH.sup.+).
[4586] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.33 (br.s, 1H, --NH);
9.06 (s, 1H); 8.85 (d, J=7.1, 1H, --NH); 8.32 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.01 (s, 2H); 4.82 (m, 1H); 4.52
(m, 1H); 4.27 (m, 1H); 4.20 (m, 1H); 3.94 (s, 2H); 3.92 (m, 1H);
3.76 (d, J=6.8, 2H); 3.30 (s, 3H); 0.87 (m, 1H); 0.28 (m, 2H); 0.09
(m, 2H).
Example 42
3-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidin-7-yl]-methanoyl}-amino)-azetidine-1-carboxylic acid ethyl
ester
[4587] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid azetidin-3-ylamide (example A172) and ethyl
chloroformate the title compound is obtained as colorless
solid.
[4588] MS (ESI): m/z=479 (MH.sup.+).
[4589] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --NH);
9.06 (s, 1H); 8.84 (d, J=7.1, 1H, --NH); 8.31 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.01 (s, 2H); 4.79 (m, 1H); 4.26
(m, 2H); 4.04 (qu, J=7.1, 2H), 3.96 (m, 2H); 3.76 (d, J=6.8, 2H);
1.19 (t, J=7.1, 3H); 0.87 (m, 1H); 0.28 (m, 2H); 0.09 (m, 2H).
Example 43
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-formyl-piperidin-4-yl)-amide
[4590] Starting from
4-(5-cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A138)
and acetic formic anhydride the title compound is obtained as
colorless solid.
[4591] MS (ESI): m/z=464 (MH.sup.+).
[4592] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.03 (s, 1H); 8.46 (d, J=7.8, 1H, --NH); 8.30 (s, 1H); 8.03 (s,
1H); 7.00 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.17
(m, 1H); 4.06 (m, 1H); 3.76 (d, J=6.7, 2H); 3.70 (m, 1H); 3.24 (m,
1H); 2.95 (m, 1H); 2.01 (m, 2H); 1.52 (m, 1H); 1.41 (m, 1H); 0.86
(m, 1H); 0.30 (m, 2H); 0.10 (m, 2H).
Example 44
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide
[4593] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-piperidin-3-ylamide (example A148) and
propionyl chloride the title compound is obtained as colorless
solid.
[4594] MS (ESI): m/z=492 (MH.sup.+, 100%).
[4595] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.00 (s, 1H); 8.56 (d, J=7.8, 0.5H, --NH); 8.51 (d, J=7.8, 0.5H);
8.30 (s, 0.5H); 8.29 (s, 0.5H); 7.00 (d, J=8.6, 1H); 6.56 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.00 (m, 1H); 3.94 (m, 0.5H); 3.76 (d,
J=6.8, 2H & m, 0.5H); 3.57 (m, 1H); 3.40 (m, 1.5H); 3.26 (m,
0.5H); 2.38 (m, 1H); 2.31 (m, 1H); 1.97 (m, 1H); 1.74 (m, 2H); 1.53
(m, 1H); 1.01 (t, J=7.3, 1.5H); 0.95 (t, J=7.3, 1.5H); 0.87 (m,
1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 45
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide
[4596] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-piperidin-3-ylamide (example A148) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4597] MS (ESI): m/z=508.0 (MH.sup.+).
[4598] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.30 (br.s, 1H, --NH);
9.00 (s, 1H); 8.55 (m, 1H, --NH); 8.31 (s, 0.5H); 8.29 (s, 0.5H);
7.00 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.13-4.00
(m, 3H); 3.91 (m, 0.5H); 3.76 (d, J=6.8, 2H); 3.68 (m, 0.5H); 3.50
(m, 1.5H); 3.35 (m, 1.5H); 3.29 (br.s, 0.5H); 3.17 (br.s, 1.5H);
1.98 (m, 1H); 1.75 (m, 2H); 1.58 (m, 1H); 0.87 (m, 1H); 0.29 (m,
2H); 0.10 (m, 2H).
Example 46
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide
[4599] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-piperidin-3-ylamide (example A148) and
acetyl chloride the title compound is obtained as colorless
solid.
[4600] MS (ESI): m/z=478.1 (MH.sup.+).
[4601] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.26 (br.s, 1H, --NH);
9.01 (s, 0.5H); 9.00 (s, 0.5H); 8.58 (d, J=7.8, 0.5H, --NH); 8.52
(d, J=7.8, 0.5H); 8.31 (s, 0.5H); 8.28 (s, 0.5H); 7.01 (d, J=8.6,
1H); 6.56 (d, J=8.6, 1H); 6.01 (s, 2H); 3.99 (m, 1H); 3.95 (m,
0.5H); 3.76 (d, J=6.8, 2H); 3.71 (m, 0.5H); 3.48 (m, 2H); 3.42 (m,
0.5H); 3.23 (m, 0.5H); 2.06 (s, 1.5H); 1.97 (s, 1.5H); 1.94 (m,
1H); 1.71 (m, 2H); 1.54 (m, 1H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10
(m, 2H).
Example 47
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide
[4602] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride (example
A149) and propionyl chloride the title compound is obtained as
colorless solid.
[4603] MS (ESI): m/z=436 (MH.sup.+, 100%).
[4604] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.85 (br.s, 1H, --NH);
9.38 (br.m, 2H, --NH.sub.2.sup.+); 9.13 (s, 1H); 8.60 (s, 1H); 8.51
(d, J=7.6, 1H, --NH); 7.06 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H);
6.05 (s, 2H); 4.31 (m, 1H); 3.79 (d, J=6.7, 2H); 3.38 (m, 1H); 3.18
(m, 1H); 2.97 (m, 1H); 2.91 (m, 1H); 2.04-11.71 (m, 4H); 0.90 (m,
1H); 0.31 (m, 2H); 0.14 (m, 2H).
Example 48
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide
[4605] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride (example
A149) and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4606] MS (ESI): m/z=508.0 (MH.sup.+).
[4607] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.30 (br.s, 1H, --NH);
9.00 (s, 1H); 8.55 (m, 1H, --NH); 8.31 (s, 0.5H); 8.29 (s, 0.5H);
7.00 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.13-4.00
(m, 3H); 3.91 (m, 0.5H); 3.76 (d, J=6.8, 2H); 3.68 (m, 0.5H); 3.50
(m, 1.5H); 3.35 (m, 1.5H); 3.29 (br.s, 0.5H); 3.17 (br.s, 1.5H);
1.98 (m, 1H); 1.75 (m, 2H); 1.58 (m, 1H); 0.87 (m, 1H); 0.29 (m,
2H); 0.10 (m, 2H).
Example 49
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide
[4608] Starting from
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride (example
A149) and acetyl chloride the title compound is obtained as
colorless solid.
[4609] MS (ESI): m/z=478.1 (MH.sup.+).
[4610] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.26 (br.s, 1H, --NH);
9.01 (s, 0.5H); 9.00 (s, 0.5H); 8.58 (d, J=7.8, 0.5H, --NH); 8.52
(d, J=7.8, 0.5H); 8.31 (s, 0.5H); 8.28 (s, 0.5H); 7.01 (d, J=8.6,
1H); 6.56 (d, J=8.6, 1H); 6.01 (s, 2H); 3.99 (m, 1H); 3.95 (m,
0.5H); 3.76 (d, J=6.8, 2H); 3.71 (m, 0.5H); 3.48 (m, 2H); 3.42 (m,
0.5H); 3.23 (m, 0.5H); 2.06 (s, 1.5H); 1.97 (s, 1.5H); 1.94 (m,
1H); 1.71 (m, 2H); 1.54 (m, 1H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10
(m, 2H).
Example 50
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4611] Starting from
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4612] MS (ESI): m/z=522 (MH.sup.+).
[4613] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.30 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.58 (d,
J=8.2, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 3.82 (m, 1H); 3.79 (s, 2H); 3.76 (d, J=6.7, 2H); 3.70 (m,
1H); 3.31 (s, 3H); 2.00 (m, 2H); 1.81 (m, 2H); 1.44 (m, 4H); 0.86
(m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 51
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4614] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
acetyl chloride the title compound is obtained as colorless
solid.
[4615] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4616] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.00 (s, 1H); 8.38 (d, J=7.8, 1H, --NH); 8.20 (s, 1H); 7.74 (d,
J=7.7, 1H); 7.61 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 3.92 (d, J=6.9, 2H); 3.86
(s, 3H); 3.80 (m, 1H); 3.59 (m, 1H); 2.01 (m, 2H); 1.87 (m, 2H);
1.80 (s, 3H); 1.42 (m, 2H); 1.31 (m, 2H); 0.97 (m, 1H); 0.36 (m,
2H); 0.23 (m, 2H).
Example 52
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4617] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4618] MS (ESI): m/z=504 (MH.sup.+, 100%).
[4619] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.00 (s, 1H); 8.39 (d, J=7.8, 1H, --NH); 8.20 (s, 1H); 7.96 (d,
J=7.8, 1H); 7.62 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 3.92 (d, J=6.9, 2H); 3.86
(s, 3H); 3.81 (m, 1H); 3.61 (m, 1H); 2.01 (m, 2H); 1.88 (m, 2H);
1.53 (m, 1H); 1.38 (m, 4H); 0.97 (m, 1H); 0.62 (m, 4H); 0.36 (m,
2H); 0.23 (m, 2H).
Example 53
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4620] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4621] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4622] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.00 (s, 1H); 8.38 (d, J=7.8, 1H, --NH); 8.21 (s, 1H); 7.61 (d,
J=8.5, 1H); 7.59 (d, J=8.3, 1H, --NH); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 3.91 (d, J=6.9, 2H); 3.85
(s, 3H & m, 1H); 3.78 (s, 2H); 3.68 (m, 1H); 3.31 (s, 3H); 2.01
(m, 2H); 1.81 (m, 2H); 1.44 (m, 4H); 0.97 (m, 1H); 0.36 (m, 2H);
0.23 (m, 2H).
Example 54
trans-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4623] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4624] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4625] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.00 (s, 1H); 8.38 (d, J=7.9, 1H, --NH); 8.21 (s, 1H); 7.62 (d,
J=8.5, 1H); 7.03 (d, J=7.6, 1H, --NH); 6.73 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 3.98 (qu, J=7.0, 2H); 3.92
(d, J=6.9, 2H); 3.86 (s, 3H); 3.79 (m, 1H); 3.69 (m, 1H); 2.01 (m,
2H, 1.82 (m, 2H); 1.46 (m, 4H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23
(m, 2H).
Example 55
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4626] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
acetyl chloride the title compound is obtained as colorless
solid.
[4627] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4628] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
9.03 (s, 1H); 8.63 (d, J=7.7, 1H, --NH); 8.21 (s, 1H); 7.87 (d,
J=7.6, 1H, --NH); 7.61 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 4.02 (m, 1H); 3.91 (d,
J=6.9, 2H); 3.86 (s, 3H); 3.76 (m, 1H); 1.87-1.55 (m, 9H); 0.97 (m,
1H); 0.65 (m, 4H); 0.37 (m, 2H); 0.23 (m, 2H).
Example 56
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4629] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4630] MS (ESI): m/z=504 (MH.sup.+, 100%).
[4631] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
9.03 (s, 1H); 8.68 (d, J=7.6, 1H, --NH); 8.21 (s, 1H); 8.08 (d,
J=7.6, 1H, --NH); 7.61 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 4.03 (m, 1H); 3.91 (d,
J=6.9, 2H); 3.86 (s, 3H); 3.79 (m, 1H); 1.83 (s, 1H); 1.82-1.55 (m,
8H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23 (m, 2H).
Example 57
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4632] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4633] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4634] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.03 (s, 1H); 8.68 (d, J=7.5, 1H, --NH); 8.20 (s, 1H); 7.70 (d,
J=7.7, 1H, --NH); 7.61 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 4.06 (m, 1H); 3.91 (d,
J=7.0, 2H); 3.86 (s, 3H); 3.81 (s, 2H & m, 1H); 3.31 (s, 3H);
1.86-1.59 (m, 8H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23 (m, 2H).
Example 58
cis-(4-{[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4635] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4636] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4637] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.03 (s, 1H); 8.67 (d, J=7.7, 1H, --NH); 8.20 (d, J=3.3, 1H); 7.61
(d, J=8.5, 1H); 7.22 (d, J=6.5, 1H, --NH); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 4.00 (qu, J=7.1, 2H & m,
1H); 3.91 (d, J=6.9, 2H); 3.86 (s, 3H); 3.50 (m, 1H); 1.87-1.56 (m,
8H); 1.18 (t, J=7.1, 3H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23 (m,
2H).
Example 59
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4638] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and acetyl
chloride the title compound is obtained as colorless solid.
[4639] MS (ESI): m/z=464 (MH.sup.+, 100%).
[4640] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.92 (br.s, 1H, --NH);
9.00 (s, 1H); 8.54 (d, J=7.7, 1H, --NH); 8.23 (d, J=3.2, 1H); 7.61
(d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5, J.sub.2=2.1, 1H); 6.69 (d,
J=2.1, 1H); 4.20 (m, 1H); 4.12 (m, 1H); 3.91 (d, J=7.0, 2H); 3.86
(s, 3H); 3.79 (m, 1H); 3.27 (m, 1H); 2.92 (m, 1H); 1.96 (m, 2H);
1.55 (m, 1H); 1.39 (m 1H); 0.98 (m, 1H); 0.37 (m, 2H); 0.23 (m,
2H).
Example 60
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide
[4641] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4642] MS (ESI): m/z=490 (MH.sup.+, 100%).
[4643] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.93 (br.s, 1H, --NH);
9.00 (s, 1H); 8.56 (d, J=7.8, 1H, --NH); 8.23 (d, J=2.2, 1H); 7.61
(d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5, J.sub.2=2.1, 1H); 6.69 (d,
J=2.1, 1H); 4.15 (m, 2H); 4.12 (d, J=4.4, 2H); 3.92 (d, J=7.0, 2H);
3.86 (s, 3H); 3.75 (m, 1H); 3.31 (s, 3H); 3.21 (m, 1H); 2.96 (m,
1H); 1.97 (m, 2H); 1.54 (m, 1H); 1.41 (m 1H); 0.98 (m, 1H); 0.37
(m, 2H); 0.23 (m, 2H).
Example 61
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide
[4644] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4645] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4646] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.92 (br.s, 1H, --NH);
9.00 (s, 1H); 8.53 (d, J=7.8, 1H, --NH); 8.23 (d, J=3.0, 1H); 7.61
(d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5, J.sub.2=2.1, 1H); 6.69 (d,
J=2.1, 1H); 4.30-4.10 (m, 3H); 3.92 (d, J=7.0, 2H); 3.86 (s, 3H);
3.39 (m, 1H); 2.97 (m, 1H); 2.10-1.89 (m, 2H); 1.53 (m, 1H); 1.41
(m, 1H); 0.98 (m, 1H); 0.74 (m, 4H); 0.38 (m, 2H); 0.23 (m,
2H).
Example 62
4-({1-[4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
n-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester
[4647] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and ethyl
chloroformate the title compound is obtained as colorless
solid.
[4648] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4649] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
9.00 (s, 1H); 8.57 (d, J=7.6, 1H, --NH); 8.21 (s, 1H); 7.62 (d,
J=8.4, 1H); 6.73 (dd, J.sub.1=8.4, J.sub.2=2.1, 1H); 6.69 (d,
J=2.1, 1H); 4.07 (qu, J=7.1, 2H & m, 1H); 3.92 (d, J=7.1, 2H
& m, 2H); 3.86 (s, 3H); 3.10 (m, 2H); 1.96 (m, 2H); 1.49 (m,
2H); 1.20 (t, J=7.1, 1H); 0.98 (m, 1H); 0.37 (m, 2H); 0.24 (m,
2H).
Example 63
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4650] Starting from
trans-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A153) and
acetyl chloride the title compound is obtained as colorless
solid.
[4651] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4652] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.23 (s, 1H); 7.73 (d,
J=7.7, 1H, --NH); 7.19 (t, J=1.7, 1H); 7.11 (d, J=1.7, 2H); 3.82
(d, J=6.9, 2H & m, 1H); 3.77 (s, 3H); 3.57 (m, 1H); 2.02 (m,
2H); 1.87 (m, 2H); 1.79 (s, 3H); 1.53-1.20 (m, 4H); 0.92 (m, 1H);
0.32 (m, 2H); 0.15 (m, 2H).
Example 64
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4653] Starting from
trans-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A153) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4654] MS (ESI): m/z=504 (MH.sup.+, 100%).
[4655] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.23 (s, 1H); 7.94 (d,
J=7.7, 1H, --NH); 7.18 (t, J=1.7, 1H); 7.11 (d, J=1.7, 2H); 3.82
(d, J=6.9, 2H & m, 1H); 3.77 (s, 3H); 3.60 (m, 1H); 2.02 (m,
2H); 1.87 (m, 2H); 1.53 (m, 1H); 1.52-1.20 (m, 4H); 0.92 (m, 1H);
0.63 (m, 4H); 0.32 (m, 2H); 0.15 (m, 2H).
Example 65
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4656] Starting from
trans-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A153) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4657] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4658] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.05 (s, 1H); 8.35 (d, J=7.8, 1H, --NH); 8.23 (s, 1H); 7.57 (d,
J=8.2, 1H, --NH); 7.19 (t, J=1.7, 1H); 7.11 (d, J=1.7, 2H); 3.82
(d, J=6.9, 2H & m, 1H & s, 2H); 3.77 (s, 3H); 3.66 (m, 1H);
3.31 (s, 3H); 2.04 (m, 2H); 1.81 (m, 2H); 1.58-1.32 (m, 4H); 0.92
(m, 1H); 0.32 (m, 2H); 0.15 (m, 2H).
Example 66
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4659] Starting from
trans-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A153) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4660] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4661] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 11.97 (br.s, 1H, --NH);
9.05 (s, 1H); 8.35 (d, J=7.9, 1H, --NH); 8.23 (s, 1H); 7.18 (t,
J=1.7, 1H); 7.11 (d, J=1.7, 2H); 7.01 (d, J=7.8, 1H, --NH); 3.98
(qu, J=7.1, 2H); 3.82 (d, J=6.8, 2H & m, 1H); 3.77 (s, 3H);
3.38 (m, 1H); 2.02 (m, 2H); 1.89 (m, 2H); 1.52-1.23 (m, 4H); 1.16
(t, J=7.1, 3H); 0.92 (m, 1H); 0.32 (m, 2H); 0.16 (m, 2H).
Example 67
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4662] Starting from
cis-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A154) and
acetyl chloride the title compound is obtained as colorless
solid.
[4663] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4664] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.08 (s, 1H); 8.61 (d, J=7.6, 1H, --NH); 8.25 (s, 1H); 7.86 (d,
J=7.6, 1H, --NH); 7.19 (t, J=1.7, 1H); 7.12 (d, J=1.7, 2H); 4.02
(m, 1H); 3.83 (d, J=6.8, 2H); 3.77 (s, 3H & m, 1H); 1.84 (s,
3H); 1.81-1.53 (m, 8H); 0.92 (m, 1H); 0.33 (m, 2H); 0.17 (m,
2H).
Example 68
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4665] Starting from
cis-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A154) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4666] MS (ESI): m/z=504 (MH.sup.+, 100%).
[4667] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 12.01 (br.s, 1H, --NH);
9.09 (s, 1H); 8.63 (d, J=7.5, 1H, --NH); 8.25 (s, 1H); 8.07 (d,
J=7.5, 1H, --NH); 7.20 (t, J=1.7, 1H); 7.12 (d, J=1.7, 2H); 4.04
(m, 1H); 3.83 (d, J=6.8, 2H); 3.78 (s, 3H & m, 1H); 1.84 (s,
3H); 1.91-1.50 (m, 9H); 0.93 (m, 1H); 0.65 (m, 4H); 0.33 (m, 2H);
0.17 (m, 2H).
Example 69
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4668] Starting from
cis-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A154) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4669] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4670] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.08 (s, 1H); 8.64 (d, J=7.5, 1H, --NH); 8.24 (s, 1H); 7.69 (d,
J=7.6, 1H, --NH); 7.19 (t, J=1.7, 1H); 7.12 (d, J=1.7, 2H); 4.06
(m, 1H); 3.83 (d, J=6.8, 2H & s, 2H); 3.78 (s, 3H & m, 1H);
3.31 (s, 3H); 1.90-1.58 (m, 8H); 0.92 (m, 1H); 0.31 (m, 2H); 0.17
(m, 2H).
Example 70
cis-(4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4671] Starting from
cis-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A154) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4672] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4673] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.08 (s, 1H); 8.64 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.19 (t,
J=1.7, 1H & br.s, 1H, --NH); 7.12 (d, J=1.7, 2H); 4.00 (qu,
J=7.1, 2H & m, 1H); 3.83 (d, J=6.8, 2H); 3.78 (s, 3H); 3.51 (m,
1H); 1.88-1.58 (m, 8H); 1.18 (t, J=7.1, 3H); 0.93 (m, 1H); 0.33 (m,
2H); 0.17 (m, 2H).
Example 71
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4674] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and acetyl
chloride the title compound is obtained as colorless solid.
[4675] MS (ESI): m/z=464 (MH.sup.+, 100%).
[4676] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 4.21 (m, 1H); 4.14 (m, 1H); 3.83
(d, J=6.8, 2H & m, 1H); 3.77 (s, 3H); 3.27 (m, 1H); 2.92 (m,
1H); 2.04 (s, 3H); 1.97 (m, 2H); 1.56 (m, 1H); 1.40 (m, 1H); 0.92
(m, 1H); 0.32 (m, 2H); 0.16 (m, 2H).
Example 72
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide
[4677] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4678] MS (ESI): m/z=490 (MH.sup.+, 100%).
[4679] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 4.20 (m, 3H); 3.83 (d, J=6.8, 2H);
3.77 (s, 3H); 3.39 (m, 1H); 2.98 (m, 1H); 2.01 (m, 1H); 1.99 (m,
2H); 1.56 (m, 1H); 1.42 (m, 1H); 0.92 (m, 1H); 0.73 (m, 4H); 0.32
(m, 2H); 0.16 (m, 2H).
Example 73
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4680] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4681] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4682] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 4.17 (m, 2H); 4.11 (d, J=4.7, 2H);
3.83 (d, J=6.9, 2H); 3.77 (s, 3H & m, 1H); 3.31 (s, 3H); 3.21
(m, 1H); 2.94 (m, 1H); 1.97 (m, 2H); 1.56 (m, 1H); 1.41 (m, 1H);
0.91 (m, 1H); 0.32 (m, 2H); 0.17 (m, 2H).
Example 74
4-{[4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester
[4683] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and ethyl
chloroformate the title compound is obtained as colorless
solid.
[4684] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4685] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 4.08 (qu, J=7.1, 2H & m, 1H);
3.91 (m, 2H); 3.83 (d, J=6.8, 2H); 3.78 (s, 3H); 3.09 (m, 2H); 1.97
(m, 2H); 1.48 (m, 2H); 0.92 (m, 1H); 0.32 (m, 2H); 0.17 (m,
2H).
Example 75
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4686] Starting from
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide (example A156) and
acetyl chloride the title compound is obtained as colorless
solid.
[4687] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4688] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.06 (br.s, 1H, --NH);
9.07 (s, 1H); 8.62 (d, J=7.6, 1H; --NH); 8.28 (s, 1H); 7.86 (d,
J=7.6, 1H, --NH); 7.68 (dd, J.sub.1=8.5, J.sub.2=7.0, 1H); 7.08
(dd, J.sub.1=11.6, J.sub.2=2.3, 1H); 6.96 (ddd,
J.sub.1=J.sub.2=8.5, J.sub.3=2.3, 1H); 4.03 (m, 1H); 3.92 (d,
J=6.9, 2H); 3.78 (m, 1H); 1.83 (s, 3H); 1.81-1.50 (m, 8H); 0.98 (m,
1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 76
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4689] Starting from
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide (example A156) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4690] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4691] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.06 (br.s, 1H, --NH);
9.07 (s, 1H); 8.65 (d, J=7.4, 1H; --NH); 8.28 (s, 1H); 7.68 (dd,
J.sub.1=8.5, J.sub.2=7.0, 1H & br.s, 1H, --NH); 7.08 (dd,
J.sub.1=12.6, J.sub.2=2.3, 1H); 6.96 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.3, 1H); 4.05 (m, 1H); 3.92 (d, J=7.0, 2H); 3.82 (m, 1H
& s, 2H); 3.31 (s, 3H); 1.89-1.58 (m, 8H); 0.98 (m, 1H); 0.36
(m, 2H); 0.22 (m, 2H).
Example 77
cis-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4692] Starting from
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide (example A156) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4693] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4694] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.06 (s, 1H); 8.65 (d, J=7.8, 1H; --NH); 8.27 (s, 1H); 7.68 (dd,
J.sub.1=8.5, J.sub.2=7.0, 1H); 7.20 (br.s, 1H, --NH); 7.08 (dd,
J.sub.1=12.6, J.sub.2=2.3, 1H); 6.96 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.3, 1H); 4.03 (m, 1H); 4.00 (qu, J=7.1, 2H); 3.92 (d,
J=7.0, 2H); 3.50 (m, 1H); 1.88-1.53 (m, 8H); 1.17 (t, J=7.1, 3H);
0.98 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 78
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4695] Starting from
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A157) and
acetyl chloride the title compound is obtained as colorless
solid.
[4696] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4697] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.03 (s, 1H); 8.35 (d, J=7.9, 1H; --NH); 8.26 (s, 1H); 7.72 (d,
J=7.6, 1H, --NH); 7.67 (dd, J.sub.1=8.4, J.sub.2=7.1, 1H); 7.08
(dd, J.sub.1=11.5, J.sub.2=2.2, 1H); 6.96 (ddd,
J.sub.1=J.sub.2=8.4, J.sub.3=2.2, 1H); 3.92 (d, J=7.0, 2H); 3.82
(m, 1H); 3.58 (m, 1H); 2.01 (m, 2H); 1.87 (m, 2H); 1.79 (s, 3H);
1.42 (m, 2H); 1.31 (m, 2H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example 79
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4698] Starting from
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A157) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4699] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4700] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.04 (s, 1H); 8.35 (d, J=7.8, 1H; --NH); 8.27 (s, 1H); 7.67 (dd,
J.sub.1=8.4, J.sub.2=7.1, 1H); 7.56 (d, J=8.2, 1H, --NH); 7.08 (dd,
J.sub.1=11.5, J.sub.2=2.2, 1H); 6.96 (ddd, J.sub.1=J.sub.2=8.4,
J.sub.3=2.2, 1H); 3.92 (d, J=6.9, 2H); 3.79 (m, 1H & s, 2H);
3.70 (m, 1H); 3.31 (s, 3H); 2.01 (m, 2H); 1.87 (m, 2H); 1.43 (m,
4H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 80
trans-(4-{[4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4701] Starting from
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A157) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4702] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4703] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.04 (br.s, 1H, --NH);
9.03 (s, 1H); 8.34 (d, J=7.8, 1H; --NH); 8.26 (s, 1H); 7.67 (dd,
J.sub.1=8.4, J.sub.2=7.2, 1H); 7.07 (dd, J.sub.1=11.5, J.sub.2=2.2,
1H); 7.01 (d, J=7.2, 1H, --NH); 6.96 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.2, 1H); 3.98 (qu, J=7.0, 2H); 3.92 (d, J=7.0, 2H); 3.79
(m, 1H); 3.35 (m, 1H); 2.04 (m, 2H); 1.88 (m, 2H); 1.37 (m, 4H);
1.16 (t, J=7.0, 3H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 81
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid (1-acetyl-piperidin-4-yl)-amide
[4704] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A158) and
acetyl chloride the title compound is obtained as colorless
solid.
[4705] MS (ESI): m/z=452 (MH.sup.+, 100%).
[4706] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.03 (s, 1H); 8.50 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.67 (dd,
J.sub.1=8.5, J.sub.2=7.0, 1H); 7.08 (dd, J.sub.1=11.6, J.sub.2=2.3,
1H); 6.96 (ddd, J.sub.1=J2=8.5, J.sub.3=2.3, 1H); 4.27-4.06 (m,
2H); 3.92 (d, J=6.9, 2H); 3.79 (m, 1H); 3.28 (m, 1H); 2.91 (m, 1H);
2.04 (s, 3H); 1.97 (m, 2H); 1.57 (m, 1H); 1.40 (m, 1H); 0.96 (m,
1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 82
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid (1-propionyl-piperidin-4-yl)-amide
[4707] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A158) and
propionyl chloride the title compound is obtained as colorless
solid.
[4708] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4709] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.07 (br.s, 1H, --NH);
9.02 (s, 1H); 8.50 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.67 (dd,
J.sub.1=8.5, J.sub.2=7.0, 1H); 7.08 (dd, J.sub.1=11.6, J.sub.2=2.3,
1H); 6.96 (ddd, J.sub.1=J.sub.2=8.5, J.sub.3=2.3, 1H); 4.23 (m,
1H); 4.14 (m, 1H); 3.92 (d, J=7.0, 2H); 3.82 (m, 1H); 3.25 (m, 1H);
2.93 (m, 1H); 2.36 (qu, J=7.4, 2H); 1.97 (m, 2H); 1.52 (m, 1H);
1.40 (m, 1H); 1.01 (t, J=7.4, 3H); 0.96 (m, 1H); 0.37 (m, 2H); 0.22
(m, 2H).
Example 83
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4710] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A158) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4711] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4712] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.01 (s, 1H); 8.50 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.67 (dd,
J=8.5, J.sub.2=7.0, 1H); 7.08 (dd, J=11.6, J.sub.2=2.4, 1H); 6.96
(ddd, J=J.sub.2=8.5, J.sub.3=2.4, 1H); 4.17 (m, 1H); 4.12 (d,
J=2.3, 2H); 3.92 (d, J=7.0, 2H); 3.76 (m, 1H); 3.29 (s, 3H); 3.22
(m, 1H); 2.95 (m, 1H); 1.98 (m, 2H); 1.59 (m, 1H); 1.41 (m, 1H);
0.96 (m, 1H); 0.37 (m, 2H); 0.22 (m, 2H).
Example 84
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid (1-acetyl-piperidin-4-yl)-amide
[4713] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A159) and
acetyl chloride the title compound is obtained as colorless
solid.
[4714] MS (ESI): m/z=452 (MH.sup.+, 100%).
[4715] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.11 (br.s, 1H,
--NH); 9.05 (s, 1H); 8.49 (d, J=7.8, 1H, --NH); 8.31 (s, 1H); 7.44
(dd, J.sub.1=9.0, J.sub.2=3.2, 1H); 7.38 (ddd, J.sub.1=J.sub.2=9.1,
J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.1, J.sub.2=4.4, 1H);
4.28-4.07 (m, 2H); 3.88 (d, J=6.9, 2H); 3.80 (m, 1H); 3.27 (m, 1H);
2.92 (m, 1H); 2.04 (s, 3H); 1.97 (m, 2H); 1.56 (m, 1H); 1.42 (m,
1H); 0.94 (m, 1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 85
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid (1-propionyl-piperidin-4-yl)-amide
[4716] Starting from
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A159) and
propionyl chloride the title compound is obtained as colorless
solid.
[4717] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4718] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.11 (br.s, 1H,
--NH); 9.05 (s, 1H); 8.49 (d, J=7.9, 1H, --NH); 8.31 (s, 1H); 7.44
(dd, J.sub.1=8.9, J.sub.2=3.2, 1H); 7.38 (ddd, J.sub.1=J.sub.2=9.1,
J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.1, J.sub.2=4.4, 1H); 4.23 (m,
1H); 4.14 (m, 1H); 3.88 (d, J=6.9, 2H); 3.82 (m, 1H); 3.25 (m, 1H);
2.92 (m, 1H); 2.36 (qu, J=7.3, 2H); 1.97 (m, 2H); 1.54 (m, 1H);
1.40 (m, 1H); 1.01 (t, J=7.3, 3H); 0.94 (m, 1H); 0.34 (m, 2H); 0.19
(m, 2H).
Example 86
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4719] Starting from
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A159) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4720] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4721] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.11 (br.s, 1H,
--NH); 9.05 (s, 1H); 8.49 (d, J=7.7, 1H, --NH); 8.31 (s, 1H); 7.44
(dd, J.sub.1=9.0, J.sub.2=3.2, 1H); 7.38 (ddd, J.sub.1=J.sub.2=9.1,
J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.1, J.sub.2=4.4, 1H); 4.16 (m,
2H); 4.12 (d, J=2.6, 2H); 3.88 (d, J=6.9, 2H); 3.76 (m, 1H); 3.31
(s, 3H); 3.21 (m, 1H); 2.95 (m, 1H); 1.98 (m, 2H); 1.56 (m, 1H);
1.42 (m, 1H); 0.94 (m, 1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 87
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4722] Starting from
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide hydrochloride
(example A160) and acetyl chloride the title compound is obtained
as colorless solid.
[4723] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4724] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.08 (br.s, 1H,
--NH); 9.06 (s, 1H); 8.34 (d, J=7.7, 1H, --NH), 8.28 (s, 1H); 7.73
(d, J=7.7, 1H, --NH); 7.44 (dd, J.sub.1=8.9, J.sub.2=3.2, 1H); 7.38
(ddd, J.sub.1=J.sub.2=9.1, J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.1,
J.sub.2=4.4, 1H); 3.88 (d, J=6.9, 2H); 3.82 (m, 1H); 3.57 (m, 1H);
2.02 (m, 2H); 1.86 (m, 2H); 1.79 (s, 3H); 1.37 (m, 4H); 0.94 (m,
1H); 0.34 (m, 2H); 0.18 (m, 2H).
Example 88
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-propionylamino-cyclohexyl)-amide
[4725] Starting from
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide hydrochloride
(example A160) and propionyl chloride the title compound is
obtained as colorless solid.
[4726] MS (ESI): m/z=480 (MH.sup.+, 100%).
[4727] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.08 (br.s, 1H,
--NH); 9.06 (s, 1H); 8.34 (d, J=7.8, 1H, --NH), 8.28 (s, 1H); 7.63
(d, J=7.8, 1H, --NH); 7.44 (dd, J.sub.1=8.9, J.sub.2=3.2, 1H); 7.38
(ddd, J.sub.1=J.sub.2=9.2, J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.2,
J.sub.2=4.4, 1H); 3.88 (d, J=6.9, 2H); 3.82 (m, 1H); 3.58 (m, 1H);
2.06 (qu, J=7.5, 2H); 2.02 (m, 2H); 1.86 (m, 2H); 1.37 (m, 4H);
0.94 (m, 1H); 0.34 (m, 2H); 0.18 (m, 2H).
Example 89
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4728] Starting from
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide hydrochloride
(example A160) and methoxy-acetyl chloride the title compound is
obtained as colorless solid.
[4729] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4730] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.08 (br.s, 1H,
--NH); 9.06 (s, 1H); 8.33 (d, J=7.9, 1H, --NH), 8.28 (s, 1H); 7.56
(d, J=8.2, 1H, --NH); 7.43 (dd, J.sub.1=9.0, J.sub.2=3.3, 1H); 7.38
(ddd, J.sub.1=J.sub.2=9.1, J.sub.3=3.3, 1H); 7.19 (dd, J.sub.1=9.1,
J.sub.2=4.4, 1H); 3.88 (d, J=6.9, 2H); 3.82 (m, 1H & s, 2H);
3.71 (m, 1H); 3.31 (s, 3H); 2.02 (m, 2H); 1.82 (m, 2H); 1.45 (m,
4H); 0.94 (m, 1H); 0.34 (m, 2H); 0.18 (m, 2H).
Example 90
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid (4-acetylamino-cyclohexyl)-amide
[4731] Starting from
trans-4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) and acetyl
chloride the title compound is obtained as colorless solid.
[4732] MS (ESI): m/z=448 (MH.sup.+, 100%).
[4733] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.02 (s, 1H, --NH);
9.05 (s, 1H); 8.37 (d, J=7.9, 1H, --NH); 8.24 (s, 1H); 7.73 (d,
J=7.7, 1H, --NH); 7.64 (dd, J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53
(ddd, J.sub.1=8.0, J.sub.2=7.6, J.sub.3=1.7, 1H); 7.17 (dd,
J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13 (ddd, J.sub.1=J.sub.2=7.6,
J.sub.3=0.9, 1H); 3.91 (d, J=6.9, 2H); 3.82 (m, 1H); 3.69 (m, 1H);
2.01 (m, 2H); 1.83 (m, 2H); 1.80 (s, 3H); 1.48-1.24 (m, 4H); 0.96
(m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 91
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4734] Starting from
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4735] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4736] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.57 (, J=8.3, 1H, --NH); 7.53 (ddd,
J.sub.1=8.0, J.sub.2=7.6, J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0,
J.sub.2=0.9, 1H); 7.13 (ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H);
6.20 (s, 1H, --OH); 3.91 (d, J=6.9, 2H); 3.80 (s, 2H & m, 1H);
3.71 (m, 1H); 3.30 (s, 3H); 2.03 (m, 2H); 1.82 (m, 2H); 1.47 (m,
4H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 92
trans-(4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4737] Starting from
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) and ethyl
chloroformate the title compound is obtained as colorless
solid.
[4738] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4739] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.02 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 7.02 (d, J=7.4, 1H,
--NH); 3.98 (qu, J=7.0, 2H); 3.91 (d, J=6.8, 2H); 3.80 (m, 1H);
3.34 (m, 1H); 2.01 (m, 2H); 1.89 (m, 2H); 1.80 (s, 3H); 1.48 (m,
4H); 1.18 (t, J=7.0, 3H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example 93
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid [4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4740] Starting from
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) and
cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4741] MS (ESI): m/z=474 (MH.sup.+, 100%).
[4742] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (s, 1H, --NH);
9.05 (s, 1H); 8.37 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.95 (d,
J=7.8, 1H, --NH); 7.64 (dd, J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53
(ddd, J.sub.1=8.0, J.sub.2=7.6, J.sub.3=1.7, 1H); 7.17 (dd,
J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13 (ddd, J.sub.1=J.sub.2=7.6,
J.sub.3=0.9, 1H); 3.91 (d, J=6.8, 2H); 3.84 (m, 1H); 3.61 (m, 1H);
2.01 (m, 2H); 1.89 (m, 2H); 1.05 (m, 1H); 1.39 (m, 4H); 0.96 (m,
1H); 0.67 (m, 4H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 94
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-acetyl-piperidin-4-yl)-amide
[4743] Starting from
4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid piperidin-4-ylamide (example A162) and acetyl chloride the
title compound is obtained as colorless solid.
[4744] MS (ESI): m/z=434 (MH.sup.+, 100%).
[4745] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.06 (s, 1H, --NH);
9.05 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 4.21 (m, 1H); 4.17 (m,
1H); 3.91 (d, J=6.8, 2H); 3.80 (m, 1H); 3.28 (m, 1H); 2.92 (m, 1H);
2.04 (s, 3H); 1.98 (m, 2H); 1.57 (m, 1H); 1.40 (m, 1H); 0.96 (m,
1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 95
4-{[4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbonyl-
]-amino}-piperidine-1-carboxylic acid ethyl ester
[4746] Starting from
4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid piperidin-4-ylamide (example A162) and ethyl chloroformate the
title compound is obtained as colorless solid.
[4747] MS (ESI): m/z=464 (MH.sup.+, 100%).
[4748] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.05 (s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 4.13 (m, 1H); 4.08
(qu, J=7.1, 1H); 3.91 (d, J=6.8, 2H & m, 2H); 3.10 (m, 2H);
1.97 (m, 2H); 1.50 (m, 2H); 1.21 (t, J=7.1, 3H); 0.97 (m, 1H); 0.36
(m, 2H); 0.22 (m, 2H).
Example 96
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide
[4749] Starting from
4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid piperidin-4-ylamide (example A162) and cyclopropanecarbonyl
chloride the title compound is obtained as colorless solid.
[4750] MS (ESI): m/z=460 (MH.sup.+, 100%).
[4751] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.05 (s, 1H, --NH);
9.05 (s, 1H); 8.54 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 4.27-4.10 (m, 3H);
3.91 (d, J=6.8, 2H); 3.40 (m, 1H); 2.98 (m, 1H); 2.10-1.90 (m, 3H);
1.69-1.34 (m, 2H); 0.96 (m, 1H); 0.72 (m, 4H); 0.35 (m, 2H); 0.22
(m, 2H).
Example 97
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide
[4752] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A163) and propionyl chloride the title compound is obtained as
colorless solid.
[4753] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4754] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.50 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.41 (d,
J=9.8, 1H); 7.18 (d, J=13.4, 1H); 4.23 (m, 1H); 4.14 (m, 1H)); 3.85
(s, 3H & d, J=6.8, 2H); 3.84 (m, 1H); 3.24 (m, 1H); 2.93 (m,
1H); 2.36 (qu, J=7.4, 2H); 1.97 (m, 2H); 1.53 (m, 1H); 1.40 (m,
1H); 1.01 (t, J=7.4, 3H); 0.93 (m, 1H); 0.34 (m, 2H), 0.18 (m,
2H).
Example 98
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]-amide
[4755] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A163) and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4756] MS (ESI): m/z=512 (MH.sup.+, 100%).
[4757] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.50 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.41 (d,
J=9.8, 1H); 7.18 (d, J=13.4, 1H); 4.16 (m, 1H); 4.12 (d, J=2.7,
2H)); 3.85 (s, 3H & d, J=6.8, 2H); 3.77 (m, 1H); 3.31 (s, 3H);
3.22 (m, 1H); 2.95 (m, 1H); 1.98 (m, 2H); 1.54 (m, 1H); 1.44 (m,
1H); 0.92 (m, 1H); 0.34 (m, 2H), 0.17 (m, 2H).
Example 99
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4758] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A163) and acetyl chloride the title compound is obtained as
colorless solid.
[4759] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4760] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.50 (d, J=7.8, 1H; --NH); 8.29 (s, 1H); 7.41 (d,
J=9.8, 1H); 7.18 (d, J=13.4, 1H); 4.18 (m, 1H); 4.13 (m, 1H)); 3.85
(s, 3H & d, J=6.8, 2H); 3.81 (m, 1H); 3.27 (m, 1H); 2.92 (m,
1H); 2.04 (s, 3H); 1.97 (m, 2H); 1.56 (m, 1H); 1.40 (m, 1H); 0.93
(m, 1H); 0.34 (m, 2H), 0.17 (m, 2H).
Example 100
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide
[4761] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A164) and acetyl chloride the title compound is obtained
as colorless solid.
[4762] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4763] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.89 (br.s, 1H, --NH);
9.03 (s, 0.5H); 9.02 (s, 0.5H); 8.63 (d, J=7.2, 0.5H, --NH); 8.57
(d, J=8.3, 0.5H, --NH); 8.30 (s, 0.5H); 8.28 (s, 0.5H); 7.41 (d,
J=9.9, 1H); 7.18 (d, J=13.4, 1H); 4.08-3.90 (m, 1.5H); 3.87 (s, 3H
& d, J=6.8, 2H); 3.72 (m, 0.5H); 3.60-3.19 (m, 3H); 2.06 (s,
1.5H); 1.97 (s, 1.5H & m, 1H); 1.86-1.45 (m, 3H); 0.94 (m, 1H);
0.33 (m, 2H); 0.17 (m, 2H).
Example 101
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide
[4764] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A164) and propionyl chloride the title compound is
obtained as colorless solid.
[4765] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4766] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.01 (s, 1H); 8.61 (d, J=7.5, 0.5H, --NH); 8.57 (d, J=7.5, 0.5H,
--NH); 8.30 (s, 0.5H); 8.29 (s, 0.5H); 7.41 (d, J=9.9, 1H); 7.18
(d, J=13.4, 1H); 4.08-3.91 (m, 1.5H); 3.85 (s, 3H & d, J=6.7,
2H); 3.76 (m, 0.5H); 3.57 (m, 1H); 3.48-3.21 (m, 2H); 2.45-2.23 (m,
2H); 1.98 (m, 1H); 1.75 (m, 2H); 1.53 (m, 1H); 1.05-0.89 (m, 4H);
0.32 (m, 2H); 0.18 (m, 2H).
Example 102
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)piperidin-3-yl]-amide
[4767] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A164) and methoxy-acetyl chloride the title compound is
obtained as colorless solid.
[4768] MS (ESI): m/z=512 (MH.sup.+, 100%).
[4769] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.02 (s, 1H); 8.60 (br.m, 1H, --NH); 8.31 (m, 1H); 7.41 (d, J=9.8,
1H); 7.18 (d, J=13.3, 1H); 4.16-3.95 (m, 3H); 3.92 (m, 0.5H); 3.84
(s, 3H & d, J=6.8, 2H); 3.69 (m, 0.5H); 3.55-3.21 (m, 3H); 3.30
(s, 1H); 3.17 (s, 1H); 1.98 (m, 1H); 1.75 (m, 2H); 1.57 (m, 1H);
0.93 (m, 1H); 0.33 (m, 2H); 0.17 (m, 2H).
Example 103
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide
[4770] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A165) and acetyl chloride the title compound is obtained
as colorless MS (ESI): m/z=426 (MH.sup.+, 100%).
[4771] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.41 (br.s, 1H, --NH);
9.39 (br.s, 1H, --NH.sub.2); 9.11 (s, 1H); 8.69 (d, J=6.7, 1H,
--NH); 8.51 (d, J=3.3, 1H); 7.45 (d, J=9.8, 1H); 7.21 (d, J=13.3,
1H); 4.65 (m, 1H); 3.87 (d, J=6.8, 2H); 3.86 s, 3H); 3.52-3.46 (m,
1H); 3.30-3.14 (m, 1H); 2.32 (m, 1H); 2.04 (m, 1H); 0.93 (m, 1H);
0.33 (m, 2H); 0.19 (m, 2H). solid.
Example 104
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide
[4772] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A165) and propionyl chloride the title compound is
obtained as colorless solid.
[4773] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4774] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.04 (s, 1H); 8.62 (d, J=7.0, 1H, --NH); 8.59 (d, J=7.0, 0.5H,
--NH); 8.31 (d, J=1.8, 1H); 7.41 (d, J=9.6, 1H); 7.18 (d, J=13.3,
1H); 4.59 (m, 0.5H); 4.51 (m, 0.5H); 3.84 (s, 3H & d, J=4.4, 2H
& m, 0.5H); 3.70-3.58 (m, 1.5H); 3.56-3.38 (m, 1.5H); 3.30 (m,
0.5H); 2.33-2.18 (m, 1H & m, 2H); 2.06 (m, 0.5H); 1.94 (m,
0.5H); 1.00 (m, 3H); 0.92 (m, 1H); 0.33 (m, 2H); 0.17 (m, 2H).
Example 105
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide
[4775] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A165) and methoxy-acetyl chloride the title compound is
obtained as colorless solid.
[4776] MS (ESI): m/z=498 (MH.sup.+, 100%).
[4777] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.04 (s, 1H); 8.61 (d, J=7.2, 1H, --NH); 8.59 (d, J=7.2, 0.5H,
--NH); 8.31 (s, 1H); 7.41 (d, J=9.7, 1H); 7.18 (d, J=13.2, 1H);
4.59 (m, 0.5H); 4.51 (m, 0.5H); 4.10-3.97 (m, 2H); 3.84 (s, 3H
& d, J=4.4, 2H); 3.79 (m, 0.5H); 3.70 (m, 0.5H); 3.57 (m, 1H);
3.48 (m, 0.5H); 3.41-3.30 (m, 1.5H); 3.31 (s, 1.5H); 3.29 (s,
1.5H); 2.33-2.17 (m, 1H); 2.10 (m, 0.5H); 1.93 (m, 0.5H); 0.92 (m,
1H); 0.33 (m, 2H); 0.17 (m, 2H).
Example 106
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4778] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example
A139) and acetyl chloride the title compound is obtained as
colorless solid.
[4779] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4780] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.01 (s, 1H); 8.36 (d, J=7.8, 1H; --NH); 8.24 (s, 1H); 7.73 (d,
J=7.7, 1H, --NH); 7.49 (d, J=11.8, 1H); 6.93 (d, J=7.3, 1H); 3.97
(s, 3H); 3.95 (d, J=7.1, 2H); 3.81 (m, 1H); 3.58 (m, 1H); 2.01 (m,
2H); 1.86 (m, 2H); 1.79 (s, 3H); 1.36 (m, 4H); 0.97 (m, 1H); 0.36
(m, 2H); 0.21 (m, 2H).
Example 107
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4781] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example
A139) and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4782] MS (ESI): m/z=526 (MH.sup.+, 100%).
[4783] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.94 (br.s, 1H, --NH);
9.01 (s, 1H); 8.35 (d, J=7.8, 1H; --NH); 8.24 (s, 1H); 7.57 (d,
J=8.2, 1H, --NH); 7.49 (d, J=11.9, 1H); 6.93 (d, J=7.3, 1H); 3.97
(s, 3H); 3.95 (d, J=7.0, 2H); 3.79 (m, 1H & s, 2H); 3.54 (m,
1H); 3.31 (s, 3H); 2.03 (m, 2H); 1.80 (m, 2H); 1.45 (m, 4H); 0.96
(m, 1H); 0.36 (m, 2H); 0.21 (m, 2H).
Example 108
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4784] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A166) and acetyl chloride the title compound is obtained as
colorless solid.
[4785] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4786] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.01 (s, 1H); 8.51 (d, J=7.8, 1H; --NH); 8.27 (s, 1H); 7.50 (d,
J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.20 (m, 1H); 4.13 (m, 1H); 3.97
(s, 3H); 3.95 (d, J=7.1, 2H); 3.79 (m, 1H); 3.27 (m, 1H); 2.92 (m,
1H); 2.04 (s, 3H); 1.97 (m, 2H); 1.56 (m, 1H); 1.40 (m, 1H); 0.95
(m, 1H); 0.36 (m, 2H), 0.22 (m, 2H).
Example 109
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide
[4787] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A166) and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4788] MS (ESI): m/z=512 (MH.sup.+, 100%).
[4789] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.01 (s, 1H); 8.51 (d, J=7.8, 1H; --NH); 8.27 (s, 1H); 7.50 (d,
J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.16 (m, 1H); 4.12 (d, J=2.5,
2H); 3.97 (s, 3H); 3.95 (d, J=7.1, 2H); 3.76 (m, 1H); 3.31 (s, 3H);
3.22 (m, 1H); 2.95 (m, 1H); 1.98 (m, 2H); 1.55 (m, 1H); 1.40 (m,
1H); 0.96 (m, 1H); 0.36 (m, 2H), 0.22 (m, 2H).
Example 110
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide
[4790] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A166) and propionyl chloride the title compound is obtained as
colorless solid.
[4791] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4792] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.97 (br.s, 1H, --NH);
9.00 (s, 1H); 8.51 (d, J=7.8, 1H; --NH); 8.27 (s, 1H); 7.49 (d,
J=11.8, 1H); 6.93 (d, J=7.3, 1H); 4.23 (m, 1H); 4.13 (m, 1H); 3.97
(s, 3H); 3.95 (d, J=7.1, 2H); 3.83 (m, 1H); 3.24 (m, 1H); 2.93 (m,
1H); 2.36 (qu, J=7.4, 3H); 1.96 (m, 2H); 1.53 (m, 1H); 1.40 (m,
1H); 1.01 (t, J=7.4, 3H); 0.97 (m, 1H); 0.36 (m, 2H), 0.22 (m,
2H).
Example 111
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-propionyl-piperidin-3-yl)-amide
[4793] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A167) and propionyl chloride the title compound is
obtained as colorless solid.
[4794] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4795] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
8.97 (s, 1H); 8.61 (d, J=7.3, 0.5H; --NH); 8.56 (d, J=7.3, 0.5H,
--NH); 8.28 (s, 0.5H); 8.27 (s, 0.5H); 7.50 (d, J=11.9, 1H); 6.93
(d, J=7.3, 1H); 4.16 (m, 1H); 4.12 (d, J=2.5, 2H); 3.97 (s, 3H
& m, 1.5H); 3.95 (d, J=7.1, 2H); 3.77 (m, 0.5H); 3.57 (m, 1H);
3.40 (m, 1.5H); 3.27 (m, 0.5H); 2.38 (m, 1H); 2.32 (m, 1H); 1.96
(m, 1H); 1.74 (m, 2H); 1.53 (m, 1H); 0.99 (m, 3H & m, 1H); 0.36
(m, 2H), 0.21 (m, 2H).
Example 112
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide
[4796] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A167) and methoxy-acetyl chloride the title compound is
obtained as colorless solid.
Example 113
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-acetyl-piperidin-3-yl)-amide
[4797] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A167) and acetyl chloride the title compound is obtained
as colorless solid.
[4798] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4799] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
8.99 (s, 0.5H); 8.98 (s, 0.5H); 8.64 (d, J=7.3, 0.5H; --NH); 8.56
(d, J=7.3, 0.5H, --NH); 8.28 (s, 0.5H); 8.26 (s, 0.5H); 7.50 (d,
J=11.8, 1H); 6.93 (d, J=7.3, 1H); 3.97 (s, 3H & m, 1.5H); 3.94
(d, J=7.3, 2H); 3.73 (m, 0.5H); 3.49 (m, 2H); 3.41 (m, 0.5H); 3.22
(m, 0.5H); 2.05 (s, 1.5H); 1.98 (s, 1.5H & m, 1H); 1.71 (m,
2H); 1.54 (m, 1H); 0.97 (m, 1H); 0.36 (m, 2H), 0.22 (m, 2H).
Example 114
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((S)-1-propionyl-piperidin-3-yl)-amide
[4800] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (S)-piperidin-3-ylamide hydrochloride
(example A168) and propionyl chloride the title compound is
obtained as colorless solid.
[4801] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4802] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
8.97 (s, 1H); 8.61 (d, J=7.3, 0.5H; --NH); 8.56 (d, J=7.3, 0.5H,
--NH); 8.28 (s, 0.5H); 8.27 (s, 0.5H); 7.50 (d, J=11.9, 1H); 6.93
(d, J=7.3, 1H); 4.16 (m, 1H); 4.12 (d, J=2.5, 2H); 3.97 (s, 3H
& m, 1.5H); 3.95 (d, J=7.1, 2H); 3.77 (m, 0.5H); 3.57 (m, 1H);
3.40 (m, 1.5H); 3.27 (m, 0.5H); 2.38 (m, 1H); 2.32 (m, 1H); 1.96
(m, 2H); 1.74 (m, 2H); 1.53 (m, 1H); 0.99 (m, 3H & m, 1H); 0.36
(m, 1H), 0.21 (m, 2H).
Example 115
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(S)-1-(2-methoxy-ethanoyl)-piperidin-3-yl]amide
[4803] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (S)-piperidin-3-ylamide hydrochloride
(example A168) and methoxy-acetyl chloride the title compound is
obtained as colorless solid.
Example 116
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((S)-1-acetyl-piperidin-3-yl)-amide
[4804] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (S)-piperidin-3-ylamide hydrochloride
(example A168) and acetyl chloride the title compound is obtained
as colorless solid.
[4805] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4806] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
8.99 (s, 0.5H); 8.98 (s, 0.5H); 8.64 (d, J=7.3, 0.5H; --NH); 8.56
(d, J=7.3, 0.5H, --NH); 8.28 (s, 0.5H); 8.26 (s, 0.5H); 7.50 (d,
J=11.8, 1H); 6.93 (d, J=7.3, 1H); 3.97 (s, 3H & m, 1.5H); 3.94
(d, J=7.3, 2H); 3.73 (m, 0.5H); 3.49 (m, 2H); 3.41 (m, 0.5H); 3.22
(m, 0.5H); 2.05 (s, 1.5H); 1.98 (s, 1.5H & m, 1H); 1.71 (m,
2H); 1.54 (m, 1H); 0.97 (m, 1H); 0.36 (m, 2H), 0.22 (m, 2H).
Example 117
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-acetyl-pyrrolidin-3-yl)-amide
[4807] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A169) and acetyl chloride the title compound is obtained
as colorless solid.
[4808] MS (ESI): m/z=468.1 (MH.sup.+, 100%).
[4809] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.93 (br.s, 1H, --NH);
9.01 (s, 1H); 8.64 (d, J=7.1, 0.5H; --NH); 8.61 (d, J=8.6, 0.5H,
--NH); 8.29 (d, J=2.3, 1H); 7.50 (dd, J.sub.1=11.8, J.sub.2=1.3,
1H); 6.93 (d, J=7.2, 1H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 3.97 (s,
3H); 3.95 (d, J=7.0, 2H); 3.85 (m, 0.5H); 3.67-3.56 (m, 1.5H);
3.54-3.30 (m, 1.5H); 3.32 (m, 0.5H); 2.30 (m, 0.5H); 2.22 (m,
0.5H); 2.10 (m, 0.5H); 1.98 (m, 1.5H); 1.96 (m, 1.5H); 1.95 (m,
0.5H); 0.96 (m, 1H); 0.36 (m, 2H), 0.22 (m, 2H).
Example 118
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide
[4810] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A169) and propionyl chloride the title compound is
obtained as colorless solid.
[4811] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4812] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.97 (br.s, 1H, --NH);
9.00 (s, 0.5H); 8.99 (s, 0.5H); 8.64 (d, J=7.1, 0.5H; --NH); 8.61
(d, J=8.6, 0.5H, --NH); 8.29 (d, J=1.8, 1H); 7.50 (dd,
J.sub.1=11.9, J.sub.2=1.1, 1H); 6.93 (d, J=7.3, 1H); 4.61 (m,
0.5H); 4.51 (m, 0.5H); 3.97 (s, 3H); 3.95 (d, J=6.9, 2H); 3.82 (m,
0.5H); 3.65 (m, 0.5H); 3.51 (m, 0.5H); 3.42 (m, 1H); 3.33 (m,
0.5H); 2.33-2.17 (m, 3H); 2.05 (m, 0.5H); 1.93 (m, 0.5H); 0.98 (m,
1H); 0.36 (m, 2H), 0.23 (m, 2H).
Example 119
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide
[4813] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A169) and methoxy-acetyl chloride the title compound is
obtained as colorless solid.
[4814] MS (ESI): m/z=498 (MH.sup.+, 100%).
[4815] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.21 (br.s, 1H, --NH);
9.00 (s, 0.5H); 8.99 (s, 0.5H); 8.63 (d, J=7.3, 0.5H; --NH); 8.61
(d, J=7.3, 0.5H, --NH); 8.29 (s, 1H); 7.50 (dd, J.sub.1=11.8,
J.sub.2=1.0, 1H); 6.93 (d, J=7.3, 1H); 4.61 (m, 0.5H); 4.51 (m,
0.5H); 4.07-4.01 (m, 2H); 3.97 (s, 3H); 3.95 (d, J=7.0, 2H); 3.79
(m, 0.5H); 3.69 (m, 0.5H); 3.58 (m, 1H); 3.47 (m, 0.5H); 3.41-3.30
(m, 1.5H); 3.32 (m, 1.5H); 3.30 (m, 1.5H); 2.29 (m, 0.5H); 2.20 (m,
0.5H); 2.06 (m, 0.5H); 1.93 (m, 0.5H); 0.95 (m, 1H); 0.33 (m, 2H),
0.21 (m, 2H).
Example 120
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4816] Starting from
trans-4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A170) and
acetyl chloride the title compound is obtained as colorless
solid.
[4817] MS (ESI): m/z=462 (MH.sup.+, 100%).
[4818] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.96 (br.s, 1H, --NH);
9.03 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.73 (d,
J=7.7, 1H, --NH); 7.44 (d, J=1.9, 1H); 7.33 (dd, J.sub.1=8.4,
J.sub.2=1.9, 1H); 7.06 (d, J=8.4, 1H); 3.86 (d, J=6.8, 2H); 3.82
(m, 1H); 3.59 (m, 1H); 2.33 (s, 3H); 2.02 (m, 2H); 1.87 (m, 2H);
1.63 (s, 3H); 1.46-1.27 (m, 4H); 0.93 (m, 1H); 0.34 (m, 2H); 0.19
(m, 2H).
Example 121
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4819] Starting from
trans-4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A170) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4820] MS (ESI): m/z=492 (MH.sup.+, 100%).
[4821] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.96 (br.s, 1H, --NH);
9.03 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.56 (d,
J=8.2, 1H, --NH); 7.44 (d, J=1.9, 1H); 7.33 (dd, J.sub.1=8.4,
J.sub.2=1.9, 1H); 7.06 (d, J=8.4, 1H); 3.86 (d, J=6.8, 2H); 3.78
(s, 2H & m, 1H); 3.71 (m, 1H); 3.31 (s, 3H); 2.33 (s, 3H); 2.02
(m, 2H); 1.87 (m, 2H); 1.32 (m, 4H); 0.93 (m, 1H); 0.34 (m, 2H);
0.19 (m, 2H).
Example 122
trans-(4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid ethyl ester
[4822] Starting from
trans-4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A170) and
ethyl chloroformate the title compound is obtained as colorless
solid.
[4823] MS (ESI): m/z=492 (MH.sup.+, 100%).
[4824] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.96 (br.s, 1H, --NH);
9.03 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.44 (d,
J=1.9, 1H); 7.33 (dd, J.sub.1=8.4, J.sub.2=1.9, 1H); 7.06 (d,
J=8.4, 1H); 7.01 (d, J=7.1, 1H, --NH); 3.98 (qu, J=7.0, 1H); 3.86
(d, J=6.8, 2H); 3.79 (m, 1H); 3.34 (m, 1H); 2.33 (s, 3H); 2.01 (m,
2H); 1.88 (m, 2H); 1.46-1.26 (m, 4H); 1.16 (t, J=7.0, 3H); 0.93 (m,
1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 123
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid (1-acetyl-piperidin-4-yl)-amide
[4825] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A172) and acetyl
chloride the title compound is obtained as colorless solid.
[4826] MS (ESI): m/z=448 (MH.sup.+, 100%).
[4827] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.03 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.25 (s, 1H); 7.44 (d,
J=2.0, 1H); 7.33 (dd, J.sub.1=8.5, J.sub.2=2.0, 1H); 7.06 (d,
J=8.5, 1H); 4.23-4.10 (m, 2H); 3.87 (d, J=6.8, 2H); 3.80 (m, 1H);
3.27 (m, 1H); 2.92 (m, 1H); 2.33 (s, 3H); 2.04 (s, 3H); 1.97 (m,
2H); 1.56 (m, 1H); 1.39 (m, 1H); 0.93 (m, 1H); 0.34 (m, 2H); 0.19
(m, 2H).
Example 124
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4828] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A172) and methoxy-acetyl
chloride the title compound is obtained as colorless solid.
[4829] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4830] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.03 (s, 1H); 8.51 (d, J=7.9, 1H, --NH); 8.25 (s, 1H); 7.44 (d,
J=1.9, 1H); 7.33 (dd, J.sub.1=8.5, J.sub.2=1.9, 1H); 7.06 (d,
J=8.5, 1H); 4.16 (m, 2H); 4.12 (d, J=2.7, 2H); 3.87 (d, J=6.9, 2H);
3.76 (m, 1H); 3.31 (s, 3H); 3.22 (m, 1H); 2.96 (m, 1H); 2.33 (s,
3H); 1.97 (m, 2H); 1.56 (m, 1H); 1.41 (m, 1H); 0.93 (m, 1H); 0.34
(m, 2H); 0.19 (m, 2H).
Example 125
4-{[4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester
[4831] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A172) and ethyl
chloroformate the title compound is obtained as colorless
solid.
[4832] MS (ESI): m/z=478 (MH.sup.+, 100%).
[4833] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.03 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.44 (d,
J=2.1, 1H); 7.33 (dd, J.sub.1=8.5, J.sub.2=2.1, 1H); 7.06 (d,
J=8.5, 1H); 4.15-4.03 (m, 2H); 4.06 (qu, J=7.1, 2H); 3.89 (m, 2H);
3.87 (d, J=6.9, 2H); 2.67 (m, 1H); 2.33 (s, 3H); 1.96 (m, 2H); 1.48
(m, 2H); 1.20 (t, J=7.1, 3H); 0.93 (m, 1H); 0.34 (m, 2H); 0.19 (m,
2H).
Example 126
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4834] Starting from
trans-4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-amino-cyclohexyl)-amide hydrochloride
(example A173) and acetyl chloride the title compound is obtained
as colorless solid.
[4835] MS (ESI): m/z=506 (MH.sup.+).
[4836] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.02 (s, 1H); 8.29 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.73 (d,
J=7.7, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01
(s, 2H); 3.84 (d, J=6.3, 2H); 3.80 (m, 1H); 3.58 (m, 1H); 2.38 (m,
1H); 2.01 (m, 2H); 1.86 (m, 2H); 1.79 (s, 3H); 1.68 (m, 3H); 1.53
(m, 3H); 1.36 (m, 4H).
Example 127
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4837] Starting from
trans-4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-amino-cyclohexyl)-amide hydrochloride
(example A173) and cyclopropanecarbonyl chloride the title compound
is obtained as colorless solid.
[4838] MS (ESI): m/z=532 (MH.sup.+).
[4839] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.02 (s, 1H); 8.29 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.94 (d,
J=7.7, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01
(s, 2H); 3.84 (d, J=6.2, 2H); 3.80 (m, 1H); 3.60 (m, 1H); 2.39 (m,
1H); 2.02 (m, 2H); 1.88 (m, 2H); 1.69 (m, 3H); 1.51 (m, 4H); 1.39
(m, 4H); 0.63 (m, 4H).
Example 128
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-ethanoylamino)-cyclohexyl]-amide
[4840] Starting from trans-4-(5-cyclobutyl
methoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid (4-amino-cyclohexyl)-amide hydrochloride (example A173) and
methoxy-acetyl chloride the title compound is obtained as colorless
solid.
[4841] MS (ESI): m/z=536 (MH.sup.+).
[4842] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.01 (s, 1H); 8.28 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.56 (d,
J=8.2, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00
(s, 2H); 3.84 (d, J=6.2, 2H); 3.78 (s, 2H & m, 1H); 3.70 (m,
1H); 3.31 (s, 3H); 2.38 (m, 1H); 2.01 (m, 2H); 1.82 (m, 2H); 1.68
(m, 3H); 1.50 (m, 3H); 1.44 (m, 4H).
Example 129
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4843] Starting from
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A174)
and acetyl chloride the title compound is obtained as colorless
solid.
[4844] MS (ESI): m/z=492 (MH.sup.+).
[4845] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.01 (s, 1H); 8.43 (d, J=7.7, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 4.20 (m, 1H); 4.12
(m, 1H); 3.85 (d, J=6.2, 2H); 3.79 (m, 1H); 3.28 (m, 1H); 2.90 (m,
1H); 2.37 (m, 1H); 2.03 (s, 3H); 1.96 (m, 2H); 1.68 (m, 3H);
1.59-1.34 (m, 5H).
Example 130
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[1-(1-cyclopropyl-methanoyl)-piperidin-4-yl]-amide
[4846] Starting from
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A174)
and cyclopropanecarbonyl chloride the title compound is obtained as
colorless solid.
[4847] MS (ESI): m/z=518 (MH.sup.+).
[4848] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.01 (s, 1H); 8.45 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 4.27-4.10 (m, 3H);
3.85 (d, J=6.3, 2H); 3.38 (m, 1H); 2.95 (m, 1H); 2.37 (m, 1H);
2.09-1.90 (m, 3H); 1.69 (m, 3H); 1.59-1.36 (m, 5H); 0.72 (m,
4H).
Example 131
4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide
[4849] Starting from
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A174)
and methoxy-acetyl chloride the title compound is obtained as
colorless solid.
[4850] MS (ESI): m/z=522 (MH.sup.+).
[4851] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.01 (s, 1H); 8.43 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 4.24-4.08 (m, 2H);
4.11 (d, J=4.5, 2H); 3.85 (d, J=6.2, 2H); 3.76 (m, 1H); 3.31 (s,
3H); 3.21 (m, 1H); 2.93 (m, 1H); 2.37 (m, 1H); 1.98 (m, 1H); 1.68
(m, 3H); 1.58-1.37 (m, 5H).
Example 132
4-({1-[4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midin-7-yl]-methanoyl}-amino)-piperidine-1-carboxylic acid ethyl
ester
[4852] Starting from
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid piperidin-4-ylamide hydrochloride (example A174)
and ethyl chloroformate the title compound is obtained as colorless
solid.
[4853] MS (ESI): m/z=522 (MH.sup.+).
[4854] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.01 (s, 1H); 8.42 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 4.06 (qu, J=7.1, 2H
& m, 1H); 3.90 (m, 2H); 3.83 (d, J=6.2, 2H); 3.09 (m, 2H); 2.38
(m, 1H); 1.95 (m, 2H); 1.69 (m, 3H); 1.58-1.43 (m, 5H); 1.21 (t,
J=7.1, 3H).
Example 133
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid (1-propionyl-piperidin-4-yl)-amide
[4855] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A175) and propionyl chloride
the title compound was obtained as colorless solid.
[4856] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4857] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.25 (s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.23 (m, 1H); 4.12
(m, 1H); 3.95 (qu, J=7.0, 2H); 3.72 (m, 1H); 3.23 (m, 1H); 2.92 (m,
1H); 2.36 (qu, J=7.3, 2H); 1.95 (m, 2H); 1.60-1.31 (m, 2H); 1.03
(t, J=7.0, 3H); 1.01 (t, J=7.3, m, 3H).
Example 134
4-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
nyl]-amino}-piperidine-1-carboxylic acid ethyl ester
[4858] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A175) and ethyl chloroformate
the title compound was obtained as colorless solid.
[4859] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4860] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.06 (qu, J=7.1, 2H
& m, 1H); 3.95 (qu, J=6.9, 2H & m, 2H); 3.09 (m, 2H); 1.95
(m, 2H); 1.48 (m, 2H); 1.20 (t, J=7.1, 3H); 1.03 (t, J=6.9,
3H).
Example 135
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4861] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A175) and methoxy-acetyl
chloride the title compound was obtained as colorless solid.
[4862] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4863] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.99 (s, 1H, --NH);
9.02 (s, 1H); 8.45 (d, J=7.8, 1H, --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.17 (m, 2H); 4.12
(d, J=2.6, 2H); 3.95 (qu, J=6.9, 2H); 3.76 (m, 1H); 3.31 (s, 3H);
3.22 (m, 1H); 2.95 (m, 1H); 1.98 (m, 2H); 1.63-1.37 (m, 2H); 1.03
(t, J=6.9, 3H).
Example 136
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide
[4864] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A176) and propionyl
chloride the title compound was obtained as colorless solid.
[4865] MS (ESI): m/z=452 (MH.sup.+, 100%).
[4866] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.19 (s, 1H, --NH);
9.02 (s, 1H); 8.58 (d, J=7.2, 0.5H, --NH); 8.55 (d, J=6.9, 0.5H,
--NH); 8.32 (s, 1H); 7.02 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.01
(s, 2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 3.96 (qu, J=6.9, 2H); 3.82
(m, 0.5H); 3.71-3.32 (m, 3.5H); 2.36-2.16 (m, 3H); 2.07 (m, 0.5H);
1.94 (m, 0.5H); 1.03 (m, 6H).
Example 137
(R)-3-{[4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arbonyl]-amino}-pyrrolidine-1-carboxylic acid ethyl ester
[4867] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A176) and ethyl
chloroformate the title compound was obtained as colorless
solid.
[4868] MS (ESI): m/z=468 (MH.sup.+, 100%).
[4869] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.26 (s, 1H, --NH);
9.02 (s, 1H); 8.56 (d, J=7.0, 1H, --NH); 8.31 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.01 (s, 2H); 4.53 (m, 1H); 4.05
(qu, J=7.0, 2H); 3.95 (qu, J=6.9, 2H); 3.67 (m, 1H); 3.48 (m, 2H);
3.31 (m, 1H); 2.23 (m, 1H); 1.98 (m, 1H); 1.19 (t, J=7.0, 3H); 1.03
(t, J=6.9, 3H).
Example 138
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [(R)-1-(2-methoxy-acetyl)-pyrrolidin-amide
[4870] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A176) and methoxy-acetyl
chloride the title compound was obtained as colorless solid.
[4871] MS (ESI): m/z=468 (MH.sup.+, 100%).
[4872] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.89 (s, 1H, --NH);
9.02 (s, 1H); 8.57 (d, J=6.7, 0.5H, --NH); 8.54 (d, J=6.3, 0.5H);
8.31 (s, 1H); 7.02 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s,
2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 4.08 (d, J=3.8, 1H); 4.01 (d,
J=1.4, 2H); 3.97 (qu, J=6.9, 2H); 3.80 (m, 0.5H); 3.70 (m, 0.5H);
3.62-3.33 (m, 3H); 3.32 (s, 1.5H); 3.30 (s, 1.5H); 2.32-2.14 (m,
1H); 2.07 (m, 0.5H); 1.92 (m, 0.5H); 1.03 (t, J=6.9, 3H).
Example 139
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (1-propionyl-piperidin-4-yl)-amide
[4873] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid piperidin-4-ylamide (example A177) and propionyl chloride
the title compound was obtained as colorless solid.
[4874] MS (ESI): m/z=480 (MH.sup.+, 100%).
[4875] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.28 (s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.7, 1H, --NH); 8.28 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.24 (m, 1H); 4.14
(m, 1H); 3.85 (t, J=6.3, 2H & m, 1H); 3.24 (m, 1H); 2.92 (m,
1H); 2.36 (qu, J=7.4, 2H); 1.97 (m, 2H); 1.53 (m, 1H); 1.42 (m, 2H
& m, 1H); 1.01 (t, J=7.4, 3H); 0.63 (t, J=7.4, 3H).
Example 140
4-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carb-
onyl]-amino}-piperidine-1-carboxylic acid ethyl ester
[4876] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid piperidin-4-ylamide (example A177) and ethyl chloroformate
the title compound was obtained as colorless solid.
[4877] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4878] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
9.02 (s, 1H); 8.43 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.47 (m, 1H); 4.06
(qu, J=7.0, 2H & m, 1H); 3.91 (m, 2H); 3.85 (t, J=6.4, 2H);
3.09 (m, 2H); 1.95 (m, 2H); 1.49 (m, 2H); 1.42 (m, 2H); 1.20 (t,
J=7.0, 3H); 0.63 (t, J=7.4, 3H).
Example 141
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide
[4879] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (R)-pyrrolidin-3-ylamide (example A178) and propionyl
chloride the title compound was obtained as colorless solid.
[4880] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4881] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.25 (s, 1H, --NH);
9.02 (s, 1H); 8.57 (d, J=7.2, 0.5H, --NH); 8.54 (d, J=6.9, 0.5H,
--NH); 8.30 (s, 1H); 7.02 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.01
(s, 2H); 4.61 (m, 0.5H); 4.51 (m, 0.5H); 3.86 (t, J=6.4, 2H);
3.71-3.32 (m, 4H); 2.37-2.15 (m, 3H); 2.07 (m, 0.5H); 1.94 (m,
0.5H); 1.41 (m, 2H); 1.00 (m, 3H); 0.62 (t, J=7.4, 3H).
Example 142
(R)-3-{[4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7--
carbonyl]amino}-pyrrolidine-1-carboxylic acid ethyl ester
[4882] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (R)-pyrrolidin-3-ylamide (example A178) and ethyl
chloroformate the title compound was obtained as colorless
solid.
[4883] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4884] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.32 (s, 1H, --NH);
9.02 (s, 1H); 8.55 (d, J=7.8, 1H, --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.01 (s, 2H); 4.52 (m, 1H); 4.05
(qu, J=7.0, 2H); 3.84 (t, J=6.4, 2H); 3.67 (m, 1H); 3.47 (m, 2H);
3.30 (m, 1H); 2.23 (m, 1H); 2.00 (m, 1H); 1.41 (m, 2H); 1.19 (t,
J=7.0, 3H); 0.62 (t, J=7.4, 3H).
Example 143
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-(2-methoxy-acetyl)-pyrrolidin-3-yl]amide
[4885] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (R)-pyrrolidin-3-ylamide (example A178) and methoxy-acetyl
chloride the title compound was obtained as colorless solid.
[4886] MS (ESI): m/z=482 (MH.sup.+, 100%).
[4887] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.15 (s, 1H, --NH);
9.02 (s, 0.5H); 9.01 (s, 0.5H); 8.57 (d, J=6.8, 0.5H, --NH); 8.54
(d, J=6.3, 0.5H, --NH); 8.30 (s, 1H); 7.02 (d, J=8.6, 1H); 6.58 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.61 (m, 0.5H); 4.52 (m, 0.5H); 4.07 (d,
J=4.0, 1H); 4.01 (d, J=1.5, 1H); 3.85 (t, J=6.4, 2H); 3.80 (m,
0.5H); 3.70 (m, 0.5H); 3.62-3.34 (m, 3H); 3.32 (s, 1.5H); 3.30 (s,
1.5H); 2.34-2.15 (m, 1H); 2.07 (m, 0.5H); 1.92 (m, 0.5H); 1.41 (m,
2H); 0.62 (t, J=7.4, 3H).
Example 144
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid (1-propionyl-piperidin-4-yl)-amide
[4888] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A179) and propionyl chloride
the title compound was obtained as colorless solid.
[4889] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4890] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.29 (s, 1H, --NH);
9.01 (s, 1H); 8.43 (d, J=7.8, 1H, --NH); 8.28 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.24 (m, 1H); 4.14
(m, 1H); 3.88 (t, J=6.4, 2H); 3.86 (m, 1H); 3.24 (m, 1H); 2.92 (m,
1H); 2.36 (qu, J=7.4, 2H); 1.97 (m, 2H); 1.53 (m, 1H); 1.42 (m, 2H
& m, 1H); 1.07 (m, 2H); 1.01 (t, J=7.4, 3H); 0.69 (t, J=7.4,
3H).
Example 145
4-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
nyl]-amino}-piperidine-1-carboxylic acid ethyl ester
[4891] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A179) and ethyl chloroformate
the title compound was obtained as colorless solid.
[4892] MS (ESI): m/z=510 (MH.sup.+, 100%).
[4893] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
9.02 (s, 1H); 8.43 (d, J=7.7, 1H, --NH); 8.28 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.06 (qu, J=7.0, 2H
& m, 1H); 3.90 (t, J=6.4, 2H & m, 2H); 3.09 (m, 2H); 1.95
(m, 2H); 1.48 (m, 1H); 1.36 (m, 2H); 1.20 (t, J=7.0, 3H); 1.05 (m,
2H); 0.69 (t, J=7.4, 3H).
Example 146
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid (1-formyl-piperidin-4-yl)-amide
[4894] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A179) and acetic formic
anhydride the title compound was obtained as colorless solid.
[4895] MS (ESI): m/z=466 (MH.sup.+, 100%).
[4896] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.25 (s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.8, 1H); 8.29 (s, 1H); 8.03 (s, 1H); 7.01
(d, J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.17 (m, 1H);
4.10 (m, 1H); 3.88 (t, J=6.4, 2H); 3.53 (m, 1H); 3.26 (m, 1H); 2.95
(m, 1H); 2.00 (m, 1H); 1.52 (m, 1H); 1.39 (m, 2H & m, 1H); 1.05
(m, 2H); 0.69 (t, J=7.4, 3H).
Example 147
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid (1-propionyl-piperidin-3-yl)-amide
[4897] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-3-ylamide (example A180) and propionyl chloride
the title compound was obtained as colorless solid.
[4898] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4899] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
8.98 (s, 1H); 8.56 (d, J=7.3, 0.5H, --NH); 8.51 (d, J=7.9, 0.5H,
--NH); 8.29 (s, 0.5H); 8.28 (s, 0.5H); 7.01 (d, J=8.6, 1H); 6.59
(d, J=8.6, 1H); 6.01 (s, 2H); 4.08-3.93 (m, 1.5H); 3.88 (t, J=6.4,
2H); 3.75 (m, 0.5H); 3.54 (m, 1H); 3.50-3.35 (m, 1.5H); 3.30 (m,
0.5H); 2.37 (m, 1H); 2.30 (m, 1H); 1.97 (m, 1H); 1.74 (m, 2H); 1.56
(m, 1H); 1.39 (m, 2H); 0.99 (m, 2H & m, 3H); 0.68 (t, J=7.4,
3H).
Example 148
3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
nyl]-amino}-piperidine-1-carboxylic acid ethyl ester
[4900] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-3-ylamide (example A180) and ethyl chloroformate
the title compound was obtained as colorless solid.
[4901] MS (ESI): m/z=510 (MH.sup.+, 100%).
[4902] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (s, 1H, --NH);
8.99 (s, 1H); 8.53 (d, J=7.9, 1H, --NH); 8.28 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.01-3.92 (m, 3H);
3.88 (t, J=6.4, 2H); 3.75 (m, 1H); 3.48 (m, 1H); 3.32 (m, 2H); 1.94
(m, 1H); 1.73 (m, 2H); 1.56 (m, 1H); 1.39 (m, 2H); 1.05 (m, 2H
& m, 3H); 0.69 (t, J=7.4, 3H).
Example 149
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [1-(2-methoxy-acetyl)piperidin-3-yl]-amide
[4903] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-3-ylamide (example A180) and methoxy-acetyl
chloride the title compound was obtained as colorless solid.
[4904] MS (ESI): m/z=510 (MH.sup.+, 100%).
[4905] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.28 (s, 1H, --NH);
8.98 (s, 1H); 8.55 (br.s, 1H, --NH); 8.29 (s, 0.5H); 8.27 (s,
0.5H); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H);
4.12-3.97 (m, 3H); 3.88 (t, J=6.4, 2H & m, 0.5H); 3.68 (m,
0.5H); 3.49 (m, 1H); 3.31 (m, 2H); 3.28 (s, 1.5H); 3.16 (s, 1.5H);
1.97 (m, 1H); 1.76 (m, 2H); 1.57 (m, 1H); 1.39 (m, 2H); 1.05 (m,
2H); 0.69 (t, J=7.4, 3H).
Example 150
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid ((R)-1-propionyl-pyrrolidin-3-yl)-amide
[4906] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A181) and propionyl
chloride the title compound was obtained as colorless solid.
[4907] MS (ESI): m/z=480 (MH.sup.+, 100%).
[4908] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.01 (s, 1H); 8.57 (d, J=7.1, 1H, --NH); 8.54 (d, J=7.1, 0.5H,
--NH); 8.30 (s, 1H); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00
(s, 2H); 4.61 (m, 0.5H); 4.50 (m, 0.5H); 3.89 (t, J=6.4, 2H); 3.82
(m, 0.5H); 3.68 (m, 0.5H); 3.63-3.31 (m, 3H); 2.35-2.17 (m, 3H);
2.07 (m, 0.5H); 1.94 (m, 0.5H); 1.40 (m, 2H); 1.10-0.98 (m, 4H);
0.69 (t, J=7.4, 3H).
Example 151
(R)-3-{[4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arbonyl]amino}-pyrrolidine-1-carboxylic acid ethyl ester
[4909] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A181) and ethyl
chloroformate the title compound was obtained as colorless
solid.
[4910] MS (ESI): m/z=496 (MH.sup.+, 100%).
[4911] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --NH);
9.02 (s, 1H); 8.56 (d, J=6.7, 1H, --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H); 4.53 (m, 1H); 4.05
(qu, J=7.0, 2H); 3.88 (t, J=6.4, 2H); 3.67 (m, 1H); 3.48 (m, 2H);
3.30 (m, 1H); 2.22 (m, 1H); 1.99 (m, 1H); 1.39 (m, 2H); 1.19 (t,
J=7.0, 2H); 1.05 (m, 2H); 0.69 (t, J=7.4, 3H).
Example 152
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4912] Starting from
cis-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A183) and
acetyl chloride the title compound was obtained as colorless
solid.
[4913] MS (ESI): m/z=482 (MH.sup.+).
[4914] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.75 (br.s, 1H, --NH);
9.03 (s, 1H); 8.65 (d, J=7.6, 1H, --NH); 8.23 (d, J=3.2, 1H); 7.86
(d, J=7.6, 1H, --NH); 7.70 (d, J=8.3, 1H); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 4.24 (t, J=4.6, 2H); 4.03 (m, 1H);
3.88 (s, 3H); 3.76 (m, 1H); 3.55 (t, J=4.6, 2H); 3.13 (s, 3H); 1.83
(s, 3H); 1.80-1.63 (m, 6H); 1.60 (s, 2H).
Example 153
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4915] Starting from
cis-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A183) and
cyclopropanecarbonyl chloride the title compound was obtained as
colorless solid.
[4916] MS (ESI): m/z=508 (MH.sup.+).
[4917] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.75 (br.s, 1H, --NH);
9.04 (s, 1H); 8.67 (d, J=7.6, 1H, --NH); 8.23 (s, 1H); 8.07 (d,
J=7.6, 1H, --NH); 7.70 (d, J=8.3, 1H); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 4.24 (t, J=4.6, 2H); 4.04 (m, 1H);
3.88 (s, 3H); 3.78 (m, 1H); 3.55 (t, J=4.6, 2H); 3.13 (s, 3H);
1.86-1.54 (m, 9H); 0.65 (m, 4H).
Example 154
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4918] Starting from
cis-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A183) and
methoxy-acetyl chloride the title compound was obtained as
colorless solid.
[4919] MS (ESI): m/z=512 (MH.sup.+).
[4920] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.74 (br.s, 1H, --NH);
9.03 (s, 1H); 8.61 (d, J=7.3, 1H, --NH); 8.22 (s, 1H); 7.69 (d,
J=8.2, 1H & d, J=5.4, 1H, --NH); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.2, J.sub.2=2.2, 1H); 4.24 (t, J=4.6, 2H); 4.05 (m, 1H);
3.88 (s, 3H); 3.82 (s, 2H & m, 1H); 3.55 (t, J=4.6, 2H); 3.29
(s, 3H); 3.13 (s, 3H); 1.79 (m, 2H); 1.77-1.60 (m, 6H).
Example 155
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4921] Starting from
trans-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A182) and
acetyl chloride the title compound was obtained as colorless
solid.
[4922] MS (ESI): m/z=482 (MH.sup.+).
[4923] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.00 (s, 1H); 8.39 (d, J=7.8, 1H, --NH); 8.22 (d, J=3.4, 1H); 7.74
(d, J=7.6, 1H, --NH); 7.69 (d, J=8.2, 1H); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.2, J.sub.2=2.2, 1H); 4.24 (t, J=4.6, 2H); 3.87 (s, 3H);
3.82 (m, 1H); 3.58 (m, 1H); 3.54 (t, J=4.6, 2H); 3.13 (s, 3H); 2.01
(m, 2H); 1.88 (m, 2H); 1.63 (s, 3H); 1.42 (m, 2H); 1.31 (m,
2H).
Example 156
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(cyclopropanecarbonyl-amino)cyclohexyl]-amide
[4924] Starting from
trans-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A182) and
cyclopropanecarbonyl chloride the title compound was obtained as
colorless solid.
[4925] MS (ESI): m/z=508 (MH.sup.+).
[4926] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.00 (s, 1H); 8.40 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.95 (d,
J=7.7, 1H, --NH); 7.69 (d, J=8.3, 1H); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 4.24 (t, J=4.6, 2H); 3.87 (s, 3H);
3.82 (m, 1H); 3.61 (m, 1H); 3.54 (t, J=4.6, 2H); 3.13 (s, 3H); 2.01
(m, 2H); 1.88 (m, 2H); 1.52 (m, 1H); 1.48 (m, 4H); 0.65 (m,
4H).
Example 157
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4927] Starting from
trans-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A182) and
methoxy-acetyl chloride the title compound was obtained as
colorless solid.
[4928] MS (ESI): m/z=512 (MH.sup.+).
[4929] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.00 (s, 1H); 8.39 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.69 (d,
J=8.3, 1H); 7.58 (d, J=8.2, 1H, --NH); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 4.24 (t, J=4.6, 2H); 3.87 (s, 3H);
3.79 (s, 2H & m, 1H); 3.70 (m, 1H); 3.54 (t, J=4.6, 2H); 3.31
(s, 3H); 3.13 (s, 3H); 2.01 (m, 2H); 1.81 (m, 2H); 1.44 (m,
4H).
Example 158
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4930] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A184) and acetyl
chloride the title compound was obtained as colorless solid.
[4931] MS (ESI): m/z=468 (MH.sup.+).
[4932] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.76 (br.s, 1H, --NH);
9.00 (s, 1H); 8.56 (d, J=7.8, 1H, --NH); 8.25 (s, 1H); 7.69 (d,
J=8.3, 1H); 6.77 (s, 1H); 6.76 (dd, J.sub.1=8.3, J.sub.2=2.2, 1H);
4.24 (t, J=4.6, 2H); 4.20-4.09 (m, 3H); 3.87 (s, 3H); 3.79 (m, 1H);
3.54 (t, J=4.6, 2H); 3.27 (m, 1H); 3.13 (s, 3H); 2.91 (m, 1H); 1.97
(m, 2H); 1.56 (m, 1H); 1.40 (m, 1H).
Example 159
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (1-cyclopropanecarbonyl-piperidin-4-yl)-amide
[4933] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A184) and
cyclopropanecarbonyl chloride the title compound was obtained as
colorless solid.
[4934] MS (ESI): m/z=494 (MH.sup.+).
[4935] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.76 (br.s, 1H, --NH);
9.00 (s, 1H); 8.57 (d, J=7.7, 1H, --NH); 8.25 (d, J=3.4, 1H); 7.69
(d, J=8.2, 1H); 6.77 (s, 1H); 6.76 (dd, J.sub.1=8.2, J.sub.2=2.3,
1H); 4.24 (t, J=4.6, 2H); 4.24-4.10 (m, 3H); 3.87 (s, 3H); 3.54 (t,
J=4.6, 2H); 3.39 (m, 1H); 3.13 (s, 3H); 2.97 (m, 1H); 2.09-1.90 (m,
3H); 1.53 (m, 1H); 1.42 (m, 1H); 0.73 (m, 4H).
Example 160
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-methoxy-acetyl)-piperidin-4-yl]-amide
[4936] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A184) and
methoxy-acetyl chloride the title compound was obtained as
colorless solid.
[4937] MS (ESI): m/z=498 (MH.sup.+).
[4938] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.76 (br.s, 1H, --NH);
8.99 (s, 1H); 8.55 (d, J=7.8, 1H, --NH); 8.25 (s, 1H); 7.69 (d,
J=8.2, 1H); 6.77 (s, 1H); 6.75 (dd, J.sub.1=8.2, J.sub.2=2.2, 1H);
4.22 (t, J=4.6, 2H & m, 1H); 4.15 (m, 1H); 4.12 (d, J=4.3, 2H);
3.87 (s, 3H); 3.75 (m, 1H); 3.54 (t, J=4.6, 2H); 3.31 (s, 3H); 3.21
(m, 1H); 3.12 (s, 3H); 2.95 (m, 1H); 1.98 (m, 2H); 1.57 (m, 1H);
1.42 (m, 1H).
Example 161
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4939] Starting from
trans-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A185)
and acetyl chloride the title compound was obtained as colorless
solid.
[4940] MS (ESI): m/z=496 (MH.sup.+).
[4941] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.13 (br. s, 1H,
--NH); 9.02 (s, 1H); 8.34 (d, J=7.9, 1H, --NH); 8.26 (s, 1H); 7.73
(d, J=7.7, --NH); 7.02 (d, J=8.5, 1H); 6.61 (d, J=8.5, 1H); 6.01
(s, 2H); 4.03 (t, J=4.7, 2H); 3.83 (m, 1H); 3.56 (m, 1H); 3.39 (t,
J=4.7, 2H); 3.02 (s, 3H); 2.04 (m, 2H); 1.83 (m, 2H); 1.77 (s, 3H);
1.36 (m, 4H).
Example 162
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4942] Starting from
trans-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A185)
and cyclopropanecarbonyl chloride the title compound was obtained
as colorless solid.
[4943] MS (ESI): m/z=522 (MH.sup.+).
[4944] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.20 (br. s, 1H,
--NH); 9.02 (s, 1H); 8.34 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.90
(d, J=7.6, --NH); 7.02 (d, J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01
(s, 2H); 4.03 (t, J=4.7, 2H); 3.84 (m, 1H); 3.59 (m, 1H); 3.39 (t,
J=4.7, 2H); 3.02 (s, 3H); 2.04 (m, 2H); 1.83 (m, 2H); 1.53 (m, 1H);
1.38 (m, 4H); 0.64 (m, 4H).
Example 163
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4945] Starting from
trans-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A185)
and methoxy-acetyl chloride the title compound was obtained as
colorless solid.
[4946] MS (ESI): m/z=526 (MH.sup.+).
[4947] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.15 (br. s, 1H,
--NH); 9.02 (s, 1H); 8.33 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.57
(d, J=7.6, --NH); 7.02 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.01
(s, 2H); 4.03 (t, J=4.7, 2H); 3.78 (s, 2H & m, 2H); 3.39 (t,
J=4.7, 2H); 3.31 (s, 3H); 3.02 (s, 3H); 2.03 (m, 2H); 1.80 (m, 2H);
1.44 (m, 4H).
Example 164
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4948] Starting from
cis-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A186)
and acetyl chloride the title compound was obtained as colorless
solid.
[4949] MS (ESI): m/z=496 (MH.sup.+).
[4950] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.10 (br.s, 1H, --NH);
9.05 (s, 1H); 8.55 (d, J=7.6, 1H; --NH); 8.28 (s, 1H); 7.85 (d,
J=7.6, 1H, --NH); 7.03 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.02
(s, 2H); 4.04 (t, J=4.7, 2H); 3.76 (m, 1H); 3.39 (t, J=4.7, 2H
& m, 1H); 3.02 (s, 3H); 1.83 (s, 3H); 1.73 (m. 4H), 1.66 (m,
4H).
Example 165
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (4-acetylamino-cyclohexyl)-amide
[4951] Starting from
cis-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A186)
and cyclopropanecarbonyl chloride the title compound was obtained
as colorless solid.
[4952] MS (ESI): m/z=522 (MH.sup.+).
[4953] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.18 (br.s, 1H, --NH);
9.06 (s, 1H); 8.57 (d, J=7.6, 1H; --NH); 8.29 (s, 1H); 8.06 (d,
J=7.6, 1H, --NH); 7.03 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.02
(s, 2H); 4.04 (t, J=4.7, 2H); 3.76 (m, 1H); 3.79 (m, 1H); 3.40 (t,
J=4.7, 2H); 3.03 (s, 3H); 1.75 (m. 4H), 1.66 (m, 5H); 0.65 (m,
4H).
Example 166
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[4-(2-methoxy-acetylamino)-cyclohexyl]-amide
[4954] Starting from
cis-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A186)
and methoxy-acetyl chloride the title compound was obtained as
colorless solid.
[4955] MS (ESI): m/z=526 (MH.sup.+).
[4956] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.13 (br.s, 1H, --NH);
9.05 (s, 1H); 8.58 (d, J=7.4, 1H; --NH); 8.28 (s, 1H); 7.69 (d,
J=7.6, 1H, --NH); 7.03 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.02
(s, 2H); 4.04 (t, J=4.7, 2H & m, 1H); 3.82 (s, 2H & m, 1H);
3.39 (t, J=4.7, 2H); 3.31 (s, 3H); 3.03 (s, 3H); 1.73 (m. 8H).
Example 167
cis-[4-({4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]p-
yrimidine-7-carbonyl}-amino)-cyclohexyl]-carbamic acid ethyl
ester
[4957] Starting from
cis-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A186)
and ethyl chloroformate the title compound was obtained as
colorless solid.
[4958] MS (ESI): m/z=526 (MH.sup.+).
[4959] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.20 (br.s, 1H, --NH);
9.05 (s, 1H); 8.59 (d, J=7.8, 1H; --NH); 8.27 (s, 1H); 7.19 (d,
J=7.6, 1H, --NH); 7.03 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.02
(s, 2H); 4.04 (t, J=4.7, 2H & m, 1H); 3.99 (qu, J=7.1, 2H);
3.50 (m, 1H); 3.39 (t, J=4.7, 2H); 3.03 (s, 3H); 1.67 (m. 8H); 1.17
(t, J=7.1, 3H).
Example 168
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[4960] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid piperidin-4-ylamide (example A187) and acetyl
chloride the title compound was obtained as colorless solid.
[4961] MS (ESI): m/z=482 (MH.sup.+).
[4962] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.17 (br.s, 1H, --NH);
9.02 (s, 1H); 8.45 (d, J=7.8, 1H; --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01 (s, 2H); 4.17 (m, 2H); 4.03
(t, J=4.7, 2H); 3.80 (m, 1H); 3.39 (t, J=4.7, 2H); 3.27 (m, 1H);
3.03 (s, 3H); 2.93 (m, 1H); 2.05 (s, 3H); 1.97 (m, 2H); 1.47 (m,
2H).
Example 169
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
(1-cyclopropanecarbonyl-piperidin-4-yl)-amide
[4963] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid piperidin-4-ylamide (example A187) and
cyclopropanecarbonyl chloride the title compound was obtained as
colorless solid.
[4964] MS (ESI): m/z=508 (MH.sup.+).
[4965] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.02 (s, 1H); 8.46 (d, J=7.8, 1H; --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01 (s, 2H); 4.20 (m, 3H); 4.03
(t, J=4.7, 2H); 3.39 (t, J=4.7, 2H & m, 1H); 3.02 (s, 3H &
m, 2H); 2.00 (m, 3H); 1.49 (m, 2H); 0.73 (m, 4H).
Example 170
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[4966] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid piperidin-4-ylamide (example A187) and
methoxy-acetyl chloride the title compound was obtained as
colorless solid.
[4967] MS (ESI): m/z=512 (MH.sup.+).
[4968] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.18 (br.s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.8, 1H; --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01 (s, 2H); 4.12 (m, 2H & s,
2H); 4.03 (t, J=4.7, 2H); 3.73 (m, 1H); 3.38 (t, J=4.7, 2H); 3.31
(s, 1H); 3.28 (m, 1H); 3.02 (s, 3H); 2.95 (m, 1H); 1.98 (m, 2H);
1.52 (m, 2H).
Example 171
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide
[4969]
4-(5-Cyclopropylmethoxy-1,3-benzodioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid piperidin-4-ylamide hydrochloride from
example A138 (472 mg; 1.0 mmol) is dissolved in dry dichloromethane
(5 mL) and DBU (2.5 mmol). Acetic acid chlorocarbonylmethyl ester
(1.1 mmol) is dropped into the reaction mixture at ice bath
temperature. After complete addition stirring is continued at
ambient temperature overnight. Methanol (1 mL) is added and
stirring is continued for two hours. The volatiles are
evaporated.
[4970] The residue is dissolved in methanol (5 mL), treated with 5M
KOH (1.5 mmol) and stirred overnight at ambient temperature. The pH
of the reaction mixture is adjusted to 6-7 by addition of 2M citric
acid. The volatiles are evaporated. The residue is purified by
reversed phase preparative HPLC. The collected product fraction is
freeze-dried to yield 364 mg of the title compound as colorless
solid.
[4971] MS (ESI): m/z=494 (MH.sup.+, 100%).
[4972] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.02 (s, 1H); 8.45 (d,
J=7.8, 1H, --NH); 8.30 (s, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d,
J=8.6, 1H); 6.01 (s, 2H); 4.52 (br.s, 1H, --OH); 4.16 (m, 2H &
d, J=7.9, 2H); 3.76 (d, J=6.8, 2H); 3.69 (m, 1H); 3.19 (m, 1H);
2.98 (m, 1H); 1.98 (m, 2H); 1.56 (m, 1H); 1.43 (m, 1H); 0.87 (m,
1H); 0.29 (m, 2H); 0.10 (m, 2H).
[4973] The following compounds are obtained analogously to the
procedure described in above example 171.
Example 172
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,-
2-d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide
[4974] Starting from
trans-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[4975] MS (ESI): m/z=508 (MH.sup.+, 100%)
[4976] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.30 (d, J=7.9, 1H, --NH); 8.27 (s, 1H); 7.49 (d,
J=8.3, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 5.42 (t, J=5.5, 1H, --OH); 3.79 (m, 1H &d, J=5.5, 2H);
3.76 (d, J=6.8, 2H); 3.69 (m, 1H); 2.02 (.about.d, J .about.8.9,
2H); 1.82 (.about.d, J .about.8.8, 2H); 1.46 (m, 4H); 0.86 (m, 1H);
0.29 (m, 2H); 0.11 (m, 2H).
Example 173
trans-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,-
2-d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide
[4977] Starting from
trans-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound
is obtained as colorless solid.
[4978] MS (ESI): m/z=522 (MH.sup.+).
[4979] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.03 (s, 1H); 8.30 (d,
J=7.9, 1H, --NH); 8.27 (s, 1H); 7.44 (d, J=8.3, 1H, --NH); 7.00 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 5.45 (br.s, 1H,
--OH); 3.94 (qu, J=6.7, 1H); 3.81 (m, 1H); 3.76 (d, J=6.7, 2H);
3.63 (m, 1H); 2.02 (m, 2H); 1.81 (m, 2H); 1.44 (m, 4H); 1.22 (d,
J=6.7, 3H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 174
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid
[4-(2-hydroxy-ethanoylamino)-cyclohexyl]-amide
[4980] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[4981] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4982] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 9.06 (s, 1H); 8.59 (d,
J=7.4, 1H, --NH); 8.28 (s, 1H); 7.57 (d, J=7.7, 1H, --NH); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01 (s, 2H); 5.34 (br.s, 1H,
--OH); 4.06 (m, 1H); 3.82 (s, 2H & m, 1H); 3.77 (d, J=6.7, 2H);
1.76 (m, 4H); 1.67 (m, 4H); 0.88 (m, 1H); 0.30 (m, 2H); 0.11 (m,
2H).
Example 175
cis-[4-({1-[4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2--
d]pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propanoylamino)-cyclohexyl]-amide
[4983] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound
is obtained as colorless solid.
[4984] MS (ESI): m/z=522 (MH.sup.+, 100%).
[4985] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.06 (s, 1H); 8.58 (d, J=7.4, 1H, --NH); 8.28 (s, 1H); 7.52 (d,
J=7.8, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.01
(s, 2H); 5.37 (d, J=5.3, 1H, --OH); 4.05 (m, 1H); 3.99 (m, 1H);
3.77 (m, 1H & d, J=6.7, 2H); 1.75 (m, 4H); 1.66 (m, 4H); 1.22
(d, J=6.7, 3H); 0.87 (m, 1H); 0.30 (m, 2H); 0.11 (m, 2H).
Example 176
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)-piperidin-4-yl]amide
[4986] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A138) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid.
[4987] MS (ESI): m/z=508 (MH.sup.+, 100%).
[4988] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
9.03 (s, 1H); 8.45 (d, J=7.7, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.88 (br.s, 1H,
--OH); 4.46 (m, 1H); 4.25 (m, 1H); 4.16 (m, 1H); 3.84 (m, 1H); 3.76
(d, J=6.8, 2H); 3.16 (m, 1H); 2.96 (m, 1H); 1.99 (m, 2H); 1.56 (m,
1H); 1.42 (m, 1H); 1.21 (dd, J.sub.1=6.9, J.sub.2=6.6, 3H); 0.87
(m, 1H); 0.29 (m, 2H); 0.11 (m, 2H).
Example 177
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[4989] Starting from
trans-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A140)
and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
Example 178
cis-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[4990] Starting from
cis-4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A141)
and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
Example 179
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)methanoyl]-piperidin-4-yl}-amide
[4991] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A138) and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
Example 180
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(R)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]amide
[4992] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and acetic acid chlorocarbonyl-methyl ester the title
compound is obtained as colorless solid.
[4993] MS (ESI): m/z=480.0 (MH.sup.+).
[4994] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 1H); 8.57 (d, J=7.1, 0.5H, --NH); 8.54 (d, J=7.1, 0.5H,
--NH); 8.31 (s, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 4.62 (m, 0.5H); 4.56 (t, J=5.6, 1H, --OH & m, 0.5H);
4.06 (d, J=5.6, 1H); 4.01 (d, J=5.6, 1H); 3.76 (m, 1H); 3.53 (m,
2H); 3.37 (m, 1H); 2.32-2.18 (m, 1H); 2.07 (m, 0.5H); 1.94 (m,
0.5H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 181
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]amide
[4995] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid.
[4996] MS (ESI): m/z=494 (MH.sup.+).
[4997] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.02 (s, 0.5H); 9.00 (s, 0.5H); 8.58 (d, J=7.1, 1H, --NH); 8.31 (s,
1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.92
(d, J=6.7, 0.5H, --OH); 4.86 (d, J=6.7, 0.5H, --OH); 4.61 (m,
0.5H); 4.53 (m, 0.5H); 4.33 (m, 0.5H); 4.26 (m, 0.5H); 3.84 (m,
0.5H); 3.76 (d, J=6.7, 2H); 3.75-3.45 (m, 3H); 3.37 (m, 0.5H); 2.24
(m, 1H); 2.07 (m, 0.5H); 1.96 (m, 0.5H); 1.23 (d, J=6.6, 1.5H);
1.20 (d, J=6.6, 1.5H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m,
2H).
Example 182
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{(R)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide
[4998] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride (example
A142) and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
Example 183
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(S)-1-(2-hydroxy-ethanoyl)-pyrrolidin-3-yl]amide
[4999] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and acetic acid chlorocarbonyl-methyl ester the title
compound is obtained as colorless solid.
[5000] MS (ESI): m/z=480.0 (MH.sup.+).
[5001] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 1H); 8.57 (d, J=7.1, 0.5H, --NH); 8.54 (d, J=7.1, 0.5H,
--NH); 8.31 (s, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 4.62 (m, 0.5H); 4.56 (t, J=5.6, 1H, --OH & m, 0.5H);
4.06 (d, J=5.6, 1H); 4.01 (d, J=5.6, 1H); 3.76 (m, 1H); 3.53 (m,
2H); 3.37 (m, 1H); 2.32-2.18 (m, 1H); 2.07 (m, 0.5H); 1.94 (m,
0.5H); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 184
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)-pyrrolidin-3-yl]amide
[5002] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid.
[5003] MS (ESI): m/z=494 (MH.sup.+).
[5004] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.31 (br.s, 1H, --NH);
9.03 (s, 0.5H); 9.01 (s, 0.5H); 8.57 (d, J=7.0, 0.5H, --NH); 8.56
(d, J=6.7, 0.5H, --NH); 8.31 (s, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d,
J=8.6, 1H); 6.00 (s, 2H); 4.87 (d, J=6.8, 0.5H, --OH); 4.86 (d,
J=6.8, 0.5H, --OH); 4.57 (m, 1H); 4.29 (m, 1H); 3.96 (m, 0.5H);
3.84-3.44 (m, 3H); 3.76 (d, J=6.8, 2H); 3.38 (m, 0.5H); 2.33-2.18
(m, 1H); 2.07 (m, 0.5H); 1.96 (m, 0.5H); 1.23 (d, J=6.5, 1.5H);
1.19 (d, J=6.5, 1.5H); 0.87 (m, 1H); 0.30 (m, 2H); 0.10 (m,
2H).
Example 185
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{(S)-1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-pyrrolidin-3-yl}-amide
[5005] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-pyrrolidin-3-ylamide hydrochloride (example
A143) and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
Example 186
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-ylmethyl]-amide
[5006] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5007] MS (ESI): m/z=508 (MH.sup.+).
[5008] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.51 (t, J=6.0, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.41 (t, J=5.3, 1H,
--OH); 4.35 (m, 1H); 4.07 (m, 2H); 3.77 (d, J=6.8, 2H); 3.69 (m,
1H); 3.34 (dd, J.sub.1=J.sub.2=5.8, 2H); 2.94 (m, 1H); 2.63 (m,
1H); 1.84 (m, 1H); 1.76 (m, 2H); 1.19 (m, 1H); 1.12 (m, 1H); 0.87
(m, 1H); 0.30 (m, 2H); 0.10 (m, 2H).
Example 187
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)piperidin-4-ylmethyl]-amide
[5009] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5010] MS (ESI): m/z=522 (MH.sup.+).
[5011] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.03 (s, 1H); 8.51 (t, J=6.0, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.5, 1H); 6.57 (d, J=8.5, 1H); 6.00 (s, 2H); 4.74 (br.s, 1H,
--OH); 4.41 (m, 1H & 1H); 4.35 (m, 1H); 3.99 (m, 1H); 3.77 (d,
J=6.7, 2H); 3.35 (dd, J.sub.1=J.sub.2=6.1, 2H); 2.98 (m, 1H); 2.60
(m, 1H); 1.86 (m, 1H); 1.76 (m, 2H); 1.19 (m, 1H); 1.17 (m, 3H);
1.12 (m, 1H); 0.88 (m, 1H); 0.30 (m, 2H); 0.10 (m, 2H).
Example 188
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-ylmethyl}-amide
[5012] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-4-ylmethyl)-amide (example A144) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5013] MS (ESI): m/z=534 (MH.sup.+).
[5014] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.27 (br.s, 1H, --NH);
9.04 (s, 1H); 8.51 (t, J=6.0, 1H, --NH); 8.27 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.23 (s, 1H, --OH); 6.00 (s, 2H);
4.42 (m, 2H); 3.77 (d, J=6.8, 2H); 3.35 (dd, J.sub.1=J.sub.2=6.3,
2H); 2.818 (m, 2H); 1.86 (m, 1H); 1.76 (m, 2H); 1.20 (m, 2H); 0.88
(m, 1H & 2H); 0.74 (m, 2H); 0.30 (m, 2H); 0.11 (m, 2H).
Example 189
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(2-hydroxy-acetyl)piperidin-3-ylmethyl]-amide
[5015] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5016] MS (ESI): m/z=508 (MH.sup.+).
[5017] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.52 (br.s, 1H, --NH); 8.28 (s, 1H); 7.01 (d, J=8.6,
1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.40 (br.s, 1H, --OH); 4.29
(m, 0.5H); 4.07 (m, 2.5H); 3.77 (d, J=6.7, 2H); 3.66 (m, 0.5H);
3.56 (m, 0.5H); 3.35 (m, 2H); 2.95 (m, 0.5H); 2.82 (m, 1H); 2.58
(m, 0.5H); 1.84 (m, 1.5H); 1.68 (m, 1.5H); 1.35 (m, 2H); 0.89 (m,
1H); 0.30 (m, 2H); 0.11 (m, 2H).
Example 190
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-3-ylmethyl]-amide
[5018] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (piperidin-3-ylmethyl)-amide (example A145) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5019] MS (ESI): m/z=522 (MH.sup.+).
[5020] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.52 (br.s, 1H, --NH); 8.28 (s, 1H); 7.01 (d, J=8.6,
1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.73 (m, 1H, --OH); 4.41
(m, 1H); 4.31 (m, 0.5H); 4.19 (m, 0.5H); 3.97 (m, 0.5H); 3.83 (m,
0.5H); 3.77 (d, J=6.7, 2H); 3.35 (m, 2H); 3.01 (m, 0.5H); 2.89 (m,
0.5H); 2.66 (m, 0.5H); 2.56 (m, 0.5H); 1.87 (m, 1H); 1.69 (m, 2H);
1.35 (m, 2H); 1.16 (m, 3H); 0.89 (m, 1H); 0.30 (m, 2H); 0.11 (m,
2H).
Example 191
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-(2-hydroxy-acetyl)pyrrolidin-3-ylmethyl]-amide
[5021] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (pyrrolidin-3-ylmethyl)-amide (example A146)
and acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5022] MS (ESI): m/z=494 (MH.sup.+).
[5023] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.04 (s, 1H); 8.55 (m, 1H, --NH); 8.29 (s, 1H); 7.00 (d, J=8.6,
1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.44 (t, J=5.4, 1H, --OH);
3.99 (m, 2H); 3.77 (d, J=6.7, 2H); 3.48 (m, 4H); 3.33 (m, 1H); 3.16
(m, 1H); 2.57 (m, 1H); 2.47 (m, 1H); 2.06 (, 0.5H); 1.97 (m, 0.5H);
1.76 (m, 0.5H); 1.66 (m, 0.5H); 0.88 (m, 1H); 0.29 (m, 2H); 0.10
(m, 2H).
Example 192
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)pyrrolidin-3-ylmethyl]-amide
[5024] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (pyrrolidin-3-ylmethyl)-amide (example A146)
and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound
is obtained as colorless solid.
[5025] MS (ESI): m/z=508 (MH.sup.+).
[5026] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.05 (s, 0.5H); 9.04 (s, 0.5H); 8.54 (m, 1H, --NH); 8.29 (s, 1H);
7.01 (d, J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.00 (s, 2H); 4.77 (m,
1H, --OH); 4.24 (m, 1H); 3.77 (d, J=6.8, 2H); 3.75 (m, 0.5H);
3.64-3.38 (m, 4.5H); 3.29 (m, 0.5H); 3.13 (m, 0.5H); 2.55 (m,
0.5H); 2.47 (m, 0.5H); 2.05 (m, 0.5H); 1.97 (m, 0.5H); 1.77 (m,
0.5H); 1.66 (m, 0.5H); 1.16 (m, 3H); 0.88 (m, 1H); 0.30 (m, 2H):
0.10 (m, 2H).
Example 193
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(2-hydroxy-acetyl)morpholin-2-ylmethyl]-amide
[5027] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (morpholin-2-ylmethyl)-amide (example A147) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5028] MS (ESI): m/z=510 (MH.sup.+).
[5029] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.04 (s, 1H); 8.58 (t, J=5.7, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.59 (br.s, 1H,
--OH); 4.28 (m, 0.5H); 4.14 (m, 1.5H); 4.05 (m, 1H); 3.91 (m, 1H);
3.76 (d, J=6.7, 2H & m, 0.5H); 3.59 (m, 2.5H); 3.23 (m, 2H);
3.11 (m, 0.5H); 2.95 (m, 0.5H); 2.80 (m, 0.5H); 2.60 (m, 0.5H);
0.88 (m, 1H); 0.29 (m, 2H): 0.10 (m, 2H).
Example 194
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionyl)-morpholin-2-ylmethyl]-amide
[5030] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (morpholin-2-ylmethyl)-amide (example A147) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5031] MS (ESI): m/z=524 (MH.sup.+).
[5032] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.29 (br.s, 1H, --NH);
9.04 (s, 1H); 8.59 (t, J=5.6, 1H, --NH); 8.30 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H); 4.92 (br.s, 1H,
--OH); 4.42 (m, 1H); 4.30 (m, 0.5H); 4.16 (m, 0.5H); 4.05 (m,
0.5H); 3.91 (m, 1.5H); 3.77 (d, J=6.7, 2H); 3.59 (m, 2H); 3.49 (m,
2H); 3.15 (m, 0.5H); 2.99 (m, 0.5H); 2.77 (m, 0.5H); 2.58 (m,
0.5H); 1.18 (br.s, 3H); 0.88 (m, 1H); 0.29 (M, 2H); 0.10 (m,
2H).
Example 195
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [1-(2-hydroxy-ethanoyl)-azetidin-3-yl]-amide
[5033] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid azetidin-3-ylamide (example A172) and acetic
acid chlorocarbonyl-methyl ester the title compound is obtained as
colorless solid.
[5034] MS (ESI): m/z=466 (MH.sup.+).
[5035] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.32 (br.s, 1H, --NH);
9.06 (s, 1H); 8.86 (d, J=7.2, 1H, --NH); 8.32 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.01 (s, 2H); 4.90 (t, J=5.4, 1H,
--OH); 4.82 (m, 1H); 4.54 (m, 1H); 4.28 (m, 1H); 4.21 (m, 1H); 3.94
(d, J=5.4, 2H); 3.90 (m, 1H); 3.76 (d, J=6.7, 2H); 0.87 (m, 1H);
0.29 (M, 2H); 0.09 (m, 2H).
Example 196
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)azetidin-3-yl]-amide
[5036] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid azetidin-3-ylamide (example A172) and acetic
acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5037] MS (ESI): m/z=480 (MH.sup.+).
[5038] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.33 (br.s, 1H, --NH);
9.07 (s, 1H); 8.85 (d, J=7.2, 1H, --NH); 8.32 (s, 1H); 7.01 (d,
J=8.6, 1H); 6.57 (d, J=8.6, 1H); 6.01 (s, 2H); 5.06 (m, 1H, --OH);
4.80 (m, 1H); 4.63 (m, 1H); 4.26 (m, 1H); 4.15 (m, 1H); 3.89 (d,
J=5.4, 2H); 3.76 (d, J=6.7, 2H); 1.21 (d, J=6.7, 3H); 0.87 (m, 1H);
0.29 (M, 2H); 0.10 (m, 2H).
Example 197
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide
[5039] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (S)-piperidin-3-ylamide (example A148) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5040] MS (ESI): m/z=508.1 (MH.sup.+).
[5041] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.86 (br.s, 1H, --NH);
9.01 (s, 0.5H); 8.98 (s, 0.5H); 8.52 (d, J=7.7, 1H, --NH); 8.30
(br.s, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H);
4.76 (.about.d, 0.5H, --OH); 4.62 (.about.d, 0.5H, --OH); 4.46 (m,
1H); 4.06 (m, 0.5H); 3.92 (m, 2H); 3.76 (d, J=6.7, 2H); 3.59 (m,
0.5H); 3.38 (m, 1H); 3.20 (m, 1H); 2.96 (m, 1H); 1.99 (m, 1H); 1.76
(m, 2H); 1.52 (m, 1H); 1.24 (br.s, 3H); 0.87 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example 198
4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide
[5042] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (R)-piperidin-3-ylamide (example A149) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5043] MS (ESI): m/z=508.1 (MH.sup.+).
[5044] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.86 (br.s, 1H, --NH);
9.01 (s, 0.5H); 8.98 (s, 0.5H); 8.52 (d, J=7.7, 1H, --NH); 8.30
(br.s, 1H); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00 (s, 2H);
4.76 (.about.d, 0.5H, --OH); 4.62 (.about.d, 0.5H, --OH); 4.46 (m,
1H); 4.06 (m, 0.5H); 3.92 (m, 2H); 3.76 (d, J=6.7, 2H); 3.59 (m,
0.5H); 3.38 (m, 1H); 3.20 (m, 1H); 2.96 (m, 1H); 1.99 (m, 1H); 1.76
(m, 2H); 1.52 (m, 1H); 1.24 (br.s, 3H); 0.87 (m, 1H); 0.29 (m, 2H);
0.10 (m, 2H).
Example 199
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5045] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5046] MS (ESI): m/z=494 (MH.sup.+, 100%).
[5047] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.01 (s, 1H); 8.39 (d, J=7.9, 1H, --NH); 8.21 (s, 1H); 7.62 (d,
J=8.5, 1H); 7.49 (d, J=8.3, 1H, --NH); 6.73 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 5.42 (t, J=5.8, 1H, --OH);
3.92 (d, J=6.9, 2H); 3.86 (s, 3H & m, 1H); 3.80 (d, J=5.8, 1H);
3.33 (m, 1H); 2.01 (m, 2H, 1.82 (m, 2H); 1.38 (m, 4H); 1.17 (t,
J=7.0, 3H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23 (m, 2H).
Example 200
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5048] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5049] MS (ESI): m/z=508 (MH.sup.+, 100%).
[5050] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.01 (s, 1H); 8.39 (d, J=7.9, 1H, --NH); 8.21 (s, 1H); 7.62 (d,
J=8.5, 1H); 7.43 (d, J=8.3, 1H, --NH); 6.73 (dd, J.sub.1=8.5,
J.sub.2=2.1, 1H); 6.69 (d, J=2.1, 1H); 5.43 (d, J=5.2, 1H, --OH);
3.96 (m, 1H); 3.92 (d, J=6.9, 2H); 3.86 (s, 3H); 3.80 (m, 1H); 3.64
(m, 1H); 2.00 (m, 2H, 1.82 (m, 2H); 1.43 (m, 4H); 1.21 (d, J=6.7,
3H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23 (m, 2H).
Example 201
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5051] Starting from
trans-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A150) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5052] MS (ESI): m/z=520 (MH.sup.+, 100%).
[5053] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 11.89 (br.s, 1H, --NH);
9.00 (s, 1H); 8.37 (d, J=7.9, 1H, --NH); 8.20 (d, J=3.2, 1H); 7.61
(d, J=8.4, 1H); 7.56 (d, J=8.5, 1H, --NH); 6.72 (dd, J.sub.1=8.4,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 6.20 (s, 1H, --OH); 3.91 (d,
J=6.9, 2H); 3.86 (s, 3H); 3.81 (m, 1H); 3.70 (m, 1H); 2.01 (m, 2H);
1.82 (m, 2H); 1.47 (m, 4H); 1.02 (m, 2H); 0.97 (m, 1H); 0.83 (m,
2H); 0.34 (m, 2H); 0.24 (m, 2H).
Example 202
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5054] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5055] MS (ESI): m/z=(MH.sup.+, 100%).
[5056] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
9.03 (s, 1H); 8.68 (d, J=7.5, 1H, --NH); 8.21 (d, J=3.3, 1H); 7.62
(d, J=8.5, 1H); 7.56 (d, J=7.8, 1H, --NH); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 5.34 (t, J=5.9, 1H, --OH);
4.07 (m, 1H); 3.92 (d, J=6.9, 2H); 3.85 (s, 3H); 3.82 (d, J=5.9, 2H
& m, 1H); 1.82-1.58 (m, 8H); 1.22 (d, J=6.7, 1H); 0.97 (m, 1H);
0.37 (m, 2H); 0.23 (m, 2H).
Example 203
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5057] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5058] MS (ESI): m/z=508 (MH.sup.+, 100%).
[5059] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.03 (s, 1H); 8.67 (d, J=7.5, 1H, --NH); 8.21 (s, 1H); 7.62 (d,
J=8.4, 1H); 7.51 (d, J=7.7, 1H, --NH); 6.72 (dd, J.sub.1=8.4,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 5.37 (d, J=5.4, 1H, --OH);
4.07 (m, 1H); 3.99 (m, 1H); 3.92 (d, J=7.0, 2H); 3.87 (s, 3H); 3.76
(m, 1H); 1.82-1.58 (m, 8H); 1.22 (d, J=6.7, 1H); 0.97 (m, 1H); 0.37
(m, 2H); 0.23 (m, 2H).
Example 204
cis-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
{-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5060] Starting from
cis-4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A151) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5061] MS (ESI): m/z=520 (MH.sup.+, 100%).
[5062] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.90 (br.s, 1H, --NH);
9.04 (s, 1H); 8.37 (d, J=7.9, 1H, --NH); 8.20 (d, J=3.2, 1H); 7.61
(d, J=8.4, 1H); 7.56 (d, J=8.5, 1H, --NH); 6.72 (dd, J.sub.1=8.4,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 6.26 (s, 1H, --OH); 4.09 (m,
1H); 3.92 (d, J=7.0, 2H); 3.86 (s, 3H); 3.78 (m, 1H); 1.87-1.66 (m,
8H); 1.02 (m, 2H); 0.98 (m, 1H); 0.83 (m, 2H); 0.34 (m, 2H); 0.24
(m, 2H).
Example 205
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide
[5063] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and acetic acid
chlorocarbonyl-methyl ester the title compound is obtained as
colorless solid.
[5064] MS (ESI): m/z=480 (MH.sup.+, 100%).
[5065] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.92 (br.s, 1H, --NH);
9.00 (s, 1H); 8.53 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.62 (d,
J=8.5, 1H); 6.73 (dd, J.sub.1=8.5, J.sub.2=2.1, 1H); 6.69 (d,
J=2.1, 1H); 4.51 (t, J=5.4, 1H, --OH); 4.27-4.05 (m, 4H); 3.92 (d,
J=6.9, 2H); 3.86 (s, 3H); 3.69 (m, 1H); 3.19 (m, 1H); 2.99 (m, 1H);
2.00 (m, 2H); 1.56 (m, 1H); 1.42 (m 1H); 1.21 (m, 3H); 0.98 (m,
1H); 0.36 (m, 2H); 0.23 (m, 2H).
Example 206
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propanoyl)piperidin-4-yl]-amide
[5066] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound is obtained as
colorless solid.
[5067] MS (ESI): m/z=494 (MH.sup.+, 100%).
[5068] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.94 (br.s, 1H, --NH);
9.00 (s, 1H); 8.53 (d, J=7.7, 1H, --NH); 8.23 (s, 1H); 7.62 (d,
J=8.5, 1H); 6.73 (dd, J.sub.1=8.5, J.sub.2=2.1, 1H); 6.69 (d,
J=2.1, 1H); 4.88 (d, J=6.9, 1H, --OH); 4.46 (m, 1H); 4.26 (m, 1H);
4.18 (m, 1H); 3.98 (m, 1H); 3.93 (d, J=6.9, 2H); 3.87 (s, 3H); 3.31
(m, 1H); 2.98 (m, 1H); 1.98 (m, 2H); 1.56 (m, 1H); 1.42 (m 1H);
0.97 (m, 1H); 0.36 (m, 2H); 0.23 (m, 2H).
Example 207
4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)-methanoyl]-piperidin-4-yl}-amide
[5069] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A152) and acetic acid
1-chlorocarbonyl-cyclopropyl ester the title compound is obtained
as colorless solid.
[5070] MS (ESI): m/z=506 (MH.sup.+, 100%).
[5071] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.92 (br.s, 1H, --NH);
9.00 (s, 1H); 8.54 (d, J=7.9, 1H, --NH); 8.23 (s, 1H); 7.62 (d,
J=8.5, 1H); 6.72 (dd, J.sub.1=8.5, J.sub.2=2.2, 1H); 6.69 (d,
J=2.2, 1H); 6.31 (s, 1H, --OH); 4.28 (m, 1H); 4.17 (m, 2H); 3.91
(d, J=6.9, 2H); 3.86 (s, 3H); 3.16 (m, 2H); 1.99 (m, 2H); 1.51 (m,
2H); 0.97 (m, 1H); 0.94 (m, 2H); 0.77 (m, 2H); 0.36 (m, 2H); 0.23
(m, 2H).
Example 208
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
Starting from
cis-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A154)
and acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5072] MS (ESI): m/z=494 (MH.sup.+, 100%).
[5073] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.08 (s, 1H); 8.65 (d, J=7.8, 1H, --NH); 8.25 (s, 1H); 7.56 (d,
J=7.7, 1H, --NH); 7.19 (t, J=1.7, 1H); 7.12 (d, J=1.7, 2H); 5.33
(t, J=5.9, 1H, --OH); 4.07 (m, 1H); 3.83 (d, J=6.8, 2H & d,
J=5.9, 2H); 3.78 (s, 3H & m, 1H); 1.89-1.61 (m, 8H); 0.93 (m,
1H); 0.33 (m, 2H); 0.17 (m, 2H).
Example 209
cis-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5074] Starting from
cis-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A154) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5075] MS (ESI): m/z=520 (MH.sup.+, 100%).
[5076] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 12.00 (br.s, 1H, --NH);
9.09 (s, 1H); 8.67 (d, J=7.4, 1H, --NH); 8.24 (s, 1H); 7.56 (d,
J=7.8, 1H, --NH); 7.18 (t, J=1.6, 1H); 7.11 (d, J=1.6, 2H); 6.27
(s, 1H, --OH); 4.10 (m, 1H); 3.82 (d, J=6.8, 2H); 3.77 (s, 3H &
m, 1H); 1.85-1.68 (m, 8H); 1.07 (m, 2H); 0.91 (m, 1H); 0.83 (m,
2H); 0.32 (m, 2H); 0.17 (m, 2H).
Example 210
trans-4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
Starting from
trans-4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A153)
and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
[5077] MS (ESI): m/z=520 (MH.sup.+, 100%).
[5078] .sup.1H-NMR 200 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.05 (s, 1H); 8.35 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.56 (d,
J=8.4, 1H, --NH); 7.18 (t, J=1.6, 1H); 7.11 (d, J=1.6, 2H); 6.15
(s, 1H, --OH); 3.82 (d, J=6.8, 2H & m, 1H); 3.77 (s, 3H); 3.68
(m, 1H); 2.03 (m, 2H); 1.83 (m, 2H); 1.57-1.39 (m, 4H); 1.02 (m,
2H); 0.91 (m, 1H); 0.82 (m, 2H); 0.32 (m, 2H); 0.15 (m, 2H).
Example 211
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]-amide
[5079] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and acetic acid
chlorocarbonyl-methyl ester the title to compound is obtained as
colorless solid.
[5080] MS (ESI): m/z=480 (MH.sup.+, 100%).
[5081] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 4.52 (t, J=5.4, 1H, --OH);
4.27-4.08 (m, 4H); 3.82 (d, J=6.8, 2H); 3.77 (s, 3H); 3.69 (m, 1H);
3.20 (m, 1H); 3.00 (m, 1H); 1.99 (m, 2H); 1.58 (m, 1H); 1.43 (m,
1H); 0.91 (m, 1H); 0.32 (m, 2H); 0.17 (m, 2H).
Example 212
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5082] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound is obtained as
colorless solid.
[5083] MS (ESI): m/z=494 (MH.sup.+, 100%).
[5084] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.51 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 488 (d, J=6.9, 1H, --OH); 447 (m,
1H); 4.30-4.20 (m, 2H); 3.97 (m, 1H); 3.82 (d, J=6.9, 2H); 3.78 (s,
3H); 3.28 (m, 1H); 2.96 (m, 1H); 1.99 (m, 2H); 1.57 (m, 1H); 1.42
(m, 1H); 1.21 (m, 3H); 0.91 (m, 1H); 0.32 (m, 2H); 0.17 (m,
2H).
Example 213
4-(2-Cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide
[5085] Starting from
4-(2-cyclopropylmethoxy-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A155) and acetic acid
1-chlorocarbonyl-cyclopropyl ester the title compound is obtained
as colorless solid.
[5086] MS (ESI): m/z=506 (MH.sup.+, 100%).
[5087] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 12.01 (br.s, 1H, --NH);
9.06 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.19 (t,
J=1.6, 1H); 7.11 (d, J=1.6, 2H); 6.31 (s, 1H, --OH); 4.29 (m, 2H);
4.18 (m, 1H); 3.83 (d, J=6.9, 2H); 3.77 (s, 3H); 3.17 (m, 2H); 2.00
(m, 2H); 1.51 (m, 2H); 0.92 (m, 3H); 0.78 (m, 2H); 0.32 (m, 2H);
0.17 (m, 2H).
Example 214
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5088] Starting from
cis-4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide (example A156) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5089] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5090] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.04 (br.s, 1H, --NH);
9.07 (s, 1H); 8.65 (d, J=7.5, 1H; --NH); 8.28 (s, 1H); 7.68 (dd,
J.sub.1=8.6, J.sub.2=7.0, 1H); 7.55 (d, J=7.7, 1H, --NH); 7.09 (dd,
J.sub.1=11.6, J.sub.2=2.4, 1H); 6.97 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.4, 1H); 5.33 (t, J=5.9, 1H, --OH); 4.07 (m, 1H); 3.93 (d,
J=7.0, 2H); 3.82 (d, J=5.9, 2H & m, 1H); 1.88-1.53 (m, 8H);
0.97 (m, 1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 215
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5091] Starting from
cis-4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide (example A156) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5092] MS (ESI): m/z=496 (MH.sup.+, 100%).
[5093] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.08 (s, 1H); 8.64 (d, J=7.4, 1H; --NH); 8.28 (s, 1H); 7.68 (dd,
J.sub.1=8.4, J.sub.2=7.1, 1H); 7.50 (d, J=7.7, 1H, --NH); 7.09 (dd,
J.sub.1=11.5, J.sub.2=2.2, 1H); 6.97 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.2, 1H); 5.37 (d, J=5.4, 1H, --OH); 4.07 (m, 1H); 3.99 (m,
1H); 3.93 (d, J=6.9, 2H); 3.76 (m, 1H); 1.82-1.59 (m, 8H); 0.97 (m,
1H); 0.37 (m, 2H); 0.22 (m, 2H).
Example 216
cis-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-
-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5094] Starting from
cis-4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid (4-amino-cyclohexyl)-amide (example A156) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5095] MS (ESI): m/z=508 (MH.sup.+, 100%).
[5096] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.09 (s, 1H); 8.67 (d, J=7.4, 1H; --NH); 8.28 (s, 1H); 7.68 (dd,
J.sub.1=8.4, J.sub.2=7.0, 1H); 7.55 (d, J=7.8, 1H, --NH); 7.09 (dd,
J.sub.1=11.5, J.sub.2=2.2, 1H); 6.97 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.2, 1H); 6.25 (s, 1H, --OH); 4.09 (m, 1H); 3.93 (d, J=7.0,
2H); 3.78 (m, 1H); 1.85-1.64 (m, 8H); 1.03 (m, 2H); 0.97 (m, 1H);
0.83 (m, 2H); 0.37 (m, 2H); 0.22 (m, 2H).
Example 217
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5097] Starting from
trans-4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A157)
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5098] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5099] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.04 (s, 1H); 8.35 (d, J=7.9, 1H; --NH); 8.27 (d, J=3.3, 1H); 7.67
(dd, J.sub.1=8.4, J.sub.2=7.2, 1H); 7.47 (d, J=8.2, 1H, --NH); 7.07
(dd, J.sub.1=11.5, J.sub.2=2.2, 1H); 6.96 (ddd,
J.sub.1=J.sub.2=8.5, J.sub.3=2.2, 1H); 5.41 (t, J=5.7, 1H, --OH);
3.92 (d, J=7.0, 2H); 3.79 (d, J=5.7, 2H & m, 1H); 2.02 (m, 2H);
1.83 (m, 2H); 1.46 (m, 4H); 0.96 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example 218
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5100] Starting from
trans-4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A157) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5101] MS (ESI): m/z=496 (MH.sup.+, 100%).
[5102] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.04 (s, 1H); 8.35 (d, J=7.8, 1H; --NH); 8.27 (d, J=3.3, 1H); 7.67
(dd, J.sub.1=8.4, J.sub.2=7.2, 1H); 7.41 (d, J=8.2, 1H, --NH); 7.07
(dd, J.sub.1=11.5, J.sub.2=2.2, 1H); 6.96 (ddd,
J.sub.1=J.sub.2=8.5, J.sub.3=2.2, 1H); 5.41 (d, J=5.2, 1H, --OH);
3.92 (d, J=7.0, 2H & m, 1H); 3.781 (m, 1H); 3.64 (m, 1H); 2.03
(m, 2H); 1.81 (m, 2H); 1.44 (m, 4H); 1.21 (d, J=6.7, 3H); 0.96 (m,
1H); 0.36 (m, 2H); 0.22 (m, 2H).
Example 219
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5103] Starting from
trans-4-(2-cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A157) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5104] MS (ESI): m/z=508 (MH.sup.+, 100%).
[5105] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.05 (br.s, 1H, --NH);
9.04 (s, 1H); 8.35 (d, J=7.9, 1H; --NH); 8.27 (s, 1H); 7.67 (dd,
J.sub.1=8.4, J.sub.2=7.2, 1H); 7.56 (d, J=8.4, 1H, --NH); 7.07 (dd,
J.sub.1=11.5, J.sub.2=2.2, 1H); 6.96 (ddd, J.sub.1=J.sub.2=8.5,
J.sub.3=2.2, 1H); 6.20 (s, 1H, --OH); 3.92 (d, J=7.0, 2H); 3.83 (m,
1H); 3.68 (m, 1H); 2.03 (m, 2H); 1.81 (m, 2H); 1.44 (m, 4H); 1.02
(m, 2H); 0.96 (m, 1H); 0.82 (m, 2H); 0.36 (m, 2H); 0.22 (m,
2H).
Example 220
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]-amide
[5106] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A159) and
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5107] MS (ESI): m/z=468 (MH.sup.+, 100%).
[5108] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.11 (br.s, 1H,
--NH); 9.05 (s, 1H); 8.49 (d, J=7.7, 1H, --NH); 8.31 (s, 1H); 7.44
(dd, J.sub.1=8.9, J.sub.2=3.2, 1H); 7.38 (ddd, J.sub.1=J.sub.2=9.1,
J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.1, J.sub.2=4.4, 1H); 4.51 (t,
J=5.4, 1H, --OH); 4.18 (m, 2H); 4.13 (d, J=5.4, 2H); 3.88 (d,
J=6.9, 2H); 3.69 (m, 1H); 3.19 (m, 1H); 2.99 (m, 1H); 1.98 (m, 2H);
1.57 (m, 1H); 1.42 (m, 1H); 0.94 (m, 1H); 0.34 (m, 2H); 0.19 (m,
2H).
Example 221
4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5109] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide hydrochloride (example A159) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5110] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5111] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.11 (br.s, 1H,
--NH); 9.05 (s, 1H); 8.49 (d, J=7.7, 1H, --NH); 8.31 (s, 1H); 7.44
(dd, J.sub.1=8.9, J.sub.2=3.2, 1H); 7.38 (ddd, J.sub.1=J.sub.2=9.1,
J.sub.3=3.2, 1H); 7.19 (dd, J.sub.1=9.1, J.sub.2=4.4, 1H); 4.86 (d,
J=7.0, 1H, --OH); 4.47 (m, 1H); 4.31-4.10 (m, 2H); 3.97 (m, 1H);
3.88 (d, J=6.9, 2H); 3.28 (m, 1H); 2.97 (m, 1H); 1.99 (m, 2H); 1.55
(m, 1H); 1.44 (m, 1H); 1.20 (br.s, 3H); 0.94 (m, 1H); 0.34 (m, 2H);
0.19 (m, 2H).
Example 222
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5112] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A160)
acetic acid chlorocarbonyl-methyl ester the title compound is
obtained as colorless solid.
[5113] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5114] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.08 (br.s, 1H,
--NH); 9.06 (s, 1H); 8.34 (d, J=7.9, 1H, --NH), 8.29 (d, J=3.3,
1H); 7.47 (d, J=8.9, 1H, --NH); 7.44 (dd, J.sub.1=8.9, J.sub.2=3.3,
1H); 7.38 (ddd, J.sub.1=J.sub.2=9.2, J.sub.3=3.3, 1H); 7.19 (dd,
J.sub.1=9.2, J.sub.2=4.4, 1H); 5.39 (br.s, 1H, --OH); 3.88 (d,
J=6.9, 2H); 3.79 (m, 1H & s, 2H); 3.70 (m, 1H); 2.02 (m, 2H);
1.83 (m, 2H); 1.45 (m, 4H); 0.94 (m, 1H); 0.34 (m, 2H); 0.18 (m,
2H).
Example 223
trans-4-(2-Cyclopropylmethoxy-4-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5115] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A160) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5116] MS (ESI): m/z=496 (MH.sup.+, 100%).
[5117] .sup.1H-NMR (300 MHz, DMSO-d.sub.6,): 12.08 (br.s, 1H,
--NH); 9.06 (s, 1H); 8.34 (d, J=7.8, 1H, --NH), 8.28 (s, 1H);
7.46-7.34 (m, 3H); 7.19 (dd, J.sub.1=9.2, J.sub.2=4.4, 1H); 5.41
(d, J=5.1, 1H, --OH); 3.95 (m, 1H); 3.88 (d, J=6.9, 2H); 3.86 (m,
1H); 3.64 (m, 1H); 2.01 (m, 2H); 1.83 (m, 2H); 1.44 (m, 4H); 1.21
(d, J=6.8, 3H); 0.94 (m, 1H); 0.34 (m, 2H); 0.18 (m, 2H).
Example 224
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5118] Starting from
trans-4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) acetic acid
chlorocarbonyl-methyl ester the title compound is obtained as
colorless solid.
[5119] MS (ESI): m/z=464 (MH.sup.+, 100%).
[5120] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.8, 1H); 7.53 (ddd, J.sub.1=7.9, J.sub.2=7.6,
J.sub.3=1.8, 1H); 7.48 (d, J=8.3, 1H, --NH); 7.17 (dd, J.sub.1=7.9,
J.sub.2=0.9, 1H); 7.13 (ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H);
5.41 (t, J=5.7, 1H, --OH); 3.91 (d, J=6.9, 2H); 3.80 (d, J=5.7, 2H
& m, 1H); 3.70 (m, 1H); 2.02 (m, 2H); 1.82 (m, 2H); 1.48 (m,
4H); 0.96 (m, 1H); 0.35 (m, 2H); 0.22 (m, 2H).
Example 225
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid [4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5121] Starting from
trans-4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) and acetic
acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5122] MS (ESI): m/z=478 (MH.sup.+, 100%).
[5123] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.02 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.9, 1H, --NH); 8.24 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.8, 1H); 7.53 (ddd, J.sub.1=7.9, J.sub.2=7.6,
J.sub.3=1.8, 1H); 7.24 (d, J=8.3, 1H, --NH); 7.17 (dd, J.sub.1=7.9,
J.sub.2=0.9, 1H); 7.13 (ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H);
5.42 (d, J=5.2, 1H, --OH); 3.95 (m, 1H); 3.91 (d, J=6.9, 2H); 3.82
(m, 1H); 3.64 (m, 1H); 2.02 (m, 2H); 1.82 (m, 2H); 1.43 (m, 4H);
1.21 (d, J=6.8, 3H); 0.96 (m, 1H); 0.35 (m, 2H); 0.22 (m, 2H).
Example 226
trans-4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbox-
ylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5124] Starting from
trans-4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carbo-
xylic acid (4-amino-cyclohexyl)-amide (example A161) and acetic
acid 1-chlorocarbonyl-cyclopropyl ester the title compound is
obtained as colorless solid.
[5125] MS (ESI): m/z=490 (MH.sup.+, 100%).
[5126] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.02 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.63 (dd,
J.sub.1=7.6, J.sub.2=1.8, 1H); 7.57 (, J=8.8, 1H, --NH); 7.53 (ddd,
J.sub.1=7.9, J.sub.2=7.6, J.sub.3=1.8, 1H); 7.17 (dd, J.sub.1=7.9,
J.sub.2=0.9, 1H); 7.13 (ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H);
6.20 (s, 1H, --OH); 3.91 (d, J=6.9, 2H); 3.82 (m, 1H); 3.70 (m,
1H); 2.02 (m, 2H); 1.83 (m, 2H); 1.48 (m, 4H); 1.02 (m, 2H); 0.95
(m, 1H); 0.82 (m, 2H); 0.35 (m, 2H); 0.22 (m, 2H).
Example 227
4-(2-Cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide
[5127] Starting from
4-(2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic
acid piperidin-4-ylamide (example A162) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound is obtained as
colorless solid.
[5128] MS (ESI): m/z=464 (MH.sup.+, 100%).
[5129] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.05 (s, 1H, --NH);
9.05 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.64 (dd,
J.sub.1=7.6, J.sub.2=1.7, 1H); 7.53 (ddd, J.sub.1=8.0, J.sub.2=7.6,
J.sub.3=1.7, 1H); 7.17 (dd, J.sub.1=8.0, J.sub.2=0.9, 1H); 7.13
(ddd, J.sub.1=J.sub.2=7.6, J.sub.3=0.9, 1H); 4.87 (d, J=6.9, 1H,
--OH); 4.47 (m, 1H); 4.21 (m, 1H); 4.17 (m, 1H); 3.98 (m, 1H); 3.91
(d, J=6.8, 2H); 3.28 (m, 1H); 2.98 (m, 1H); 1.99 (m, 2H); 1.53 (m,
1H); 1.44 (m, 1H); 1.21 (br.s, 3H); 0.96 (m, 1H); 0.36 (m, 2H);
0.22 (m, 2H).
Example 228
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide
[5130] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide (example A163) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5131] MS (ESI): m/z=512 (MH.sup.+, 100%).
[5132] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.03 (br.s, 1H, --NH);
9.05 (s, 1H); 8.50 (d, J=7.8, 1H, --NH); 8.29 (s, 1H); 7.41 (d,
J=9.8, 1H); 7.18 (d, J=13.4, 1H); 4.86 (d, J=7.0, 1H, --OH); 4.47
(m, 1H); 4.20 (m, 2H); 3.97 (m, 1H); 3.85 (s, 3H & d, J=6.8,
2H); 3.30 (m, 1H); 2.97 (m, 1H); 1.99 (m, 2H); 1.53 (m, 1H); 1.44
(m, 1H); 1.21 (br.s, 3H); 0.92 (m, 1H); 0.34 (m, 2H); 0.17 (m,
2H).
Example 229
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)piperidin-3-yl]-amide
[5133] Starting from
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A164) and acetic acid chlorocarbonyl-methyl ester the
title compound is obtained as colorless solid.
[5134] MS (ESI): m/z=498 (MH.sup.+, 100%).
[5135] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.87 (br.s, 1H, --NH);
9.02 (s, 1H); 8.61 (br.m, 1H, --NH); 8.30 (s, 1H); 7.41 (d, J=9.9,
1H); 7.18 (d, J=13.3, 1H); 4.46 (br.m, 1H, --OH); 4.15 (br.s, 1H);
4.08 (br.s, 1H); 4.02 (m, 1H); 3.85 (s, 3H & d, J=6.8, 2H);
3.69-3.40 (m, 2H); 3.40-3.19 (m, 2H); 1.98 (m, 1H); 1.76 (m, 2H);
1.58 (m, 1H); 0.93 (m, 1H); 0.33 (m, 2H); 0.18 (m, 2H).
Example 230
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-piperidin-3-yl]-amide
[5136] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A164) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the
title compound is obtained as colorless solid.
[5137] MS (ESI): m/z=512 (MH.sup.+, 100%).
[5138] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.91 (br.s, 1H, --NH);
8.04 (s, 0.5H); 9.00 (s, 0.5H); 8.57 (d, J=7.7, 1H, --NH); 8.30
(br.s, 1H); 7.41 (d, J=9.8, 1H); 7.18 (d, J=13.3, 1H); 4.76
(.about.d, 0.5H, --OH); 4.62 (.about.d, 0.5H, --OH); 4.46 (m, 1H);
4.12-3.84 (m, 2.5H); 3.85 (s, 3H & d, J=6.8, 2H); 3.59 (m,
0.5H); 3.38 (m, 1H); 3.20 (m, 1H); 1.99 (m, 1H); 1.76 (m, 2H); 1.52
(m, 1H); 1.24 (br.s, 3H); 0.93 (m, 1H); 0.363 (m, 2H); 0.18 (m,
2H).
Example 231
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)-pyrrolidin-3-yl]amide
[5139] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A165) and acetic acid chlorocarbonyl-methyl ester the
title compound is obtained as colorless solid.
[5140] MS (ESI): m/z=484 (MH.sup.+, 100%).
[5141] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.35 (br.s, 1H, --NH);
9.05 (s, 1H); 8.61 (d, J=7.0, 1H, --NH); 8.59 (d, J=7.0, 0.5H,
--NH); 8.31 (s, 1H); 7.41 (d, J=9.8, 1H); 7.18 (d, J=13.4, 1H);
4.63 (m, 0.5H); 4.51 (m, 0.5H & br.s, 1H, --OH); 4.06 (s, 1H);
3.86 (s, 1H); 3.84 (s, 3H & d, J 0 4.4, 2H); 3.80-3.70 (m, 1H);
3.62-3.44 (m, 1.5H); 3.41-3.29 (m, 1.5H); 2.33-2.17 (m, 1H); 2.07
(m, 0.5H); 1.93 (m, 0.5H); 0.92 (m, 1H); 0.33 (m, 2H); 0.17 (m,
2H).
Example 232
4-(2-Cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide
[5142] Starting from
4-(2-cyclopropylmethoxy-4-fluoro-5-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A165) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the
title compound is obtained as colorless solid.
[5143] MS (ESI): m/z=498 (MH.sup.+, 100%).
[5144] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.61 (br.s, 1H, --NH);
9.04 (s, 0.5H); 9.01 (s, 0.5H); 8.61 (d, J=6.9, 1H, --NH); 8.59 (d,
J=7.0, 0.5H, --NH); 8.31 (s, 1H); 7.41 (d, J=9.8, 1H); 7.18 (d,
J=13.4, 1H); 4.91 (d, J=6.8, 0.5H, --OH); 4.86 (d, J=6.8, 0.5H,
--OH); 4.60 (m, 0.5H); 4.53 (m, 0.5H); 4.26 (m, 0.5H); 4.02 (m,
0.5H); 3.84 (s, 3H & d, J 0 4.4, 2H); 3.82-3.72 (m, 1H);
3.71-3.52 (m, 2.5H); 3.47 (m, 0.5H); 3.40-3.30 (m, 1H); 2.33-2.17
(m, 1H); 2.07 (m, 0.5H); 1.93 (m, 0.5H); 1.23 (d, J=6.6, 1.5H);
1.20 (d, J=6.6, 1.5H); 0.92 (m, 1H); 0.33 (m, 2H); 0.17 (m,
2H).
Example 233
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5145] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example
A139) and acetic acid chlorocarbonyl-methyl ester the title
compound is obtained as colorless solid.
[5146] MS (ESI): m/z=512.1 (MH.sup.+, 100%)
[5147] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.01 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.24 (d, J=2.6, 1H); 7.50
(d, J=11.8, 1H); 7.47 (d, J=8.3, 1H, --NH); 6.93 (d, J=7.3, 1H);
5.41 (t, J=5.8, 1H, --OH); 3.97 (s, 3H); 3.95 (d, J=7.1, 2H); 3.79
(m, 1H & d, J=5.8, 2H); 3.69 (m, 1H); 2.03 (m, 2H); 1.82 (m,
2H); 1.46 (m, 4H); 0.96 (m, 1H); 0.35 (m, 2H); 0.21 (m, 2H).
Example 234
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5148] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example
A139) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid.
[5149] MS (ESI): m/z=526 (MH.sup.+, 100%).
[5150] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.01 (s, 1H); 8.36 (d, J=7.9, 1H, --NH); 8.25 (s 1H); 7.50 (d,
J=11.8, 1H); 7.42 (d, J=8.3, 1H, --NH); 6.93 (d, J=7.3, 1H); 5.41
(d, J=5.2, 1H, --OH); 3.97 (s, 3H); 3.94 (d, J=7.1, 2H & m,
1H); 3.81 (m, 1H); 3.64 (m, 1H); 2.03 (m, 2H); 1.81 (m, 2H); 1.44
(m, 4H); 1.21 (d, 3H); 0.97 (m, 1H); 0.36 (m, 2H); 0.21 (m,
2H).
Example 235
trans-4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]-
pyrimidine-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5151] Starting from
trans-4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d-
]pyrimidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example
A139) and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
[5152] MS (ESI): m/z=538 (MH.sup.+, 100%).
[5153] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.01 (s, 1H); 8.36 (d, J=7.9, 1H, --NH); 8.25 (s, 1H); 7.57 (d,
J=8.4, 1H, --NH); 7.49 (d, J=11.8, 1H); 6.93 (d, J=7.3, 1H); 6.20
(s, 1H, --OH); 3.97 (s, 3H); 3.95 (d, J=7.1, 2H); 3.81 (m, 1H);
3.69 (m, 1H); 2.02 (m, 2H); 1.83 (m, 2H); 1.48 (m, 4H); 1.02 (m,
2H); 0.97 (m, 1H); 0.82 (m, 2H); 0.36 (m, 2H); 0.21 (m, 2H).
Example 236
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-(2-hydroxy-ethanoyl)-piperidin-4-yl]amide
[5154] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A166) and acetic acid chlorocarbonyl-methyl ester the title
compound is obtained as colorless solid.
[5155] MS (ESI): m/z=498 (MH.sup.+, 100%).
[5156] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.97 (br.s, 1H, --NH);
9.01 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.27 (d, J=3.3, 1H); 7.48
(d, J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.51 (t, J=5.2, 1H, --OH);
4.18 (m, 2H); 4.13 (dd, J.sub.1=J.sub.2=5.2, 2H); 3.97 (m, 3H);
3.95 (d, J=7.2, 2H); 3.69 (m, 1H); 3.19 (m, 1H); 2.99 (m, 1H); 1.98
(m, 2H); 1.56 (m, 1H); 1.45 (m, 1H); 0.97 (m, 1H); 0.36 (m, 2H);
0.22 (m, 2H).
Example 237
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-((S)-2-hydroxy-propanoyl)piperidin-4-yl]-amide
[5157] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A166) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid.
[5158] MS (ESI): m/z=512 (MH.sup.+; 100%).
[5159] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.01 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.50 (d,
J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.86 (d, J=6.9, 1H, --OH); 4.47
(m, 1H); 4.20 (m, 2H); 3.97 (s, 3H & m, 1H); 3.95 (d, J=7.1,
2H); 3.29 (m, 1H); 2.97 (m, 1H); 1.98 (m, 2H); 1.53 (m, 1H); 1.43
(m, 1H); 1.21 (br.s, 3H); 0.97 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example 238
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
{1-[1-(1-hydroxy-cyclopropyl)methanoyl]-piperidin-4-yl}-amide
[5160] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A166) and acetic acid 1-chlorocarbonyl-cyclopropyl ester the title
compound is obtained as colorless solid.
[5161] MS (ESI): m/z=524 (MH.sup.+, 100%).
[5162] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
9.02 (s, 1H); 8.53 (d, J=7.8, 1H, --NH); 8.27 (s, 1H); 7.50 (d,
J=11.8, 1H); 6.93 (d, J=7.3, 1H); 6.31 (s, 1H, --OH); 4.28 (m, 1H);
4.18 (m, 2H); 3.97 (s, 3H); 3.95 (d, J=7.2, 2H); 3.16 (m, 2H); 1.99
(m, 2H); 1.52 (m, 2H); 0.95 (m, 1H & m, 2H); 0.77 (m, 2H); 0.37
(m, 2H); 0.22 (m, 2H).
Example 239
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(S)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide
[5163] Starting from
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (S)-piperidin-3-ylamide hydrochloride
(example A168) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the
title compound is obtained as colorless solid.
[5164] MS (ESI): m/z=512 (MH.sup.+; 100%).
[5165] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
8.99 (s, 1H); 8.58 (d, J=7.7, 1H, --NH); 8.27 (br.s, 1H); 7.50 (d,
J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.87 (.about.d, 0.5H, --OH); 4.81
(.about.d, 0.5H, --OH); 4.46 (m, 1H); 4.05 (m, 0.5H); 3.97 (s, 3H);
3.94 (d, J=7.2, 2H & m, 2H); 3.70 (m, 1H); 3.34 (m, 1H); 3.14
(m, 0.5H); 1.99 (m, 1H); 1.76 (m, 2H); 1.56 (m, 1H); 1.21
(.about.d, 1.5H); 1.13 (.about.d, 1.5H); 0.97 (m, 1H); 0.36 (m,
2H); 0.21 (m, 2H).
Example 240
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propanoyl)piperidin-3-yl]-amide
[5166] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-piperidin-3-ylamide hydrochloride
(example A167) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the
title compound is obtained as colorless solid.
[5167] MS (ESI): m/z=512 (MH.sup.+; 100%).
[5168] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.98 (br.s, 1H, --NH);
8.99 (s, 0.5H); 8.96 (s, 0.5H); 8.57 (d, J=7.7, 1H, --NH); 8.27
(br.s, 1H); 7.50 (d, J=11.9, 1H); 6.93 (d, J=7.3, 1H); 4.76
(.about.d, 0.5H, --OH); 4.62 (.about.d, 0.5H, --OH); 4.46 (m, 1H);
4.06 (m, 0.5H); 3.97 (s, 3H); 3.94 (d, J=7.2, 2H & m, 2H); 3.59
(m, 0.5H); 3.38 (m, 1H); 3.20 (m, 1H); 1.98 (m, 1H); 1.76 (m, 2H);
1.52 (m, 1H); 1.24 (br.s, 3H); 0.97 (m, 1H); 0.36 (m, 2H); 0.22 (m,
2H).
Example 241
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-(2-hydroxy-acetyl)pyrrolidin-3-yl]-amide
[5169] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A169) and acetic acid chlorocarbonyl-methyl ester the
title compound is obtained as colorless solid.
[5170] MS (ESI): m/z=484 (MH.sup.+, 100%).
[5171] .sup.1H-NMR (300 MHz, DMSO-d.sub.6/MeOH-d.sub.4): 9.01 (s,
1H); 8.63 (d, J=7.3, 0.5H; --NH); 8.61 (d, J=7.3, 0.5H, --NH); 8.29
(s, 1H); 7.49 (d, J=11.8, 1H); 6.92 (d, J=7.3, 1H); 4.62 (m, 0.5H);
4.52 (m, 0.5H); 4.06 (s, 1H); 4.01 (s, 1H); 3.97 (s, 3H); 3.95 (d,
J=7.0, 2H); 3.77 (m, 1H); 3.53 (m, 1.5H); 3.36 (m, 1.5H); 2.33-2.17
(m, 1H); 2.07 (m, 0.5H); 1.93 (m, 0.5H); 0.96 (m, 1H); 0.36 (m,
2H); 0.21 (m, 2H).
Example 242
4-(2-Cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[(R)-1-((S)-2-hydroxy-propionyl)pyrrolidin-3-yl]-amide
[5172] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (R)-pyrrolidin-3-ylamide hydrochloride
(example A169) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the
title compound is obtained as colorless solid.
[5173] MS (ESI): m/z=498 (MH.sup.+, 100%).
[5174] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.86 (br.s, 1H, --NH);
9.00 (s, 0.5H); 8.97 (s, 0.5H); 8.64 (d, J=7.0, 1H; --NH); 8.28 (s,
1H); 7.50 (d, J=11.8); 6.92 (d, J=7.2, 1H); 4.91 (d, J=6.8, 0.5H,
--OH); 4.85 (d, J=6.8, 0.5H, --OH); 4.60 (m, 0.5H); 4.55 (m, 0.5H);
4.41 (m, 0.5H); 4.26 (m, 0.5H); 3.97 (s, 3H); 3.95 (d, J=7.0, 2H);
3.83 (m, 0.5H); 3.78 (m, 0.5H); 3.71-3.53 (m, 1.5H); 3.34 (m, 1H);
2.29 (m, 0.5H); 2.19 (m, 0.5H); 2.07 (m, 0.5H); 1.95 (m, 0.5H);
1.23 (d, J=6.5, 1.5H); 1.19 (d, J=6.5, 1.5H); 0.96 (m, 1H); 0.36
(m, 2H), 0.22 (m, 2H).
Example 243
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid [4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5175] Starting from
trans-4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A170) and
acetic acid chlorocarbonyl-methyl to ester the title compound is
obtained as colorless solid.
[5176] MS (ESI): m/z=478 (MH.sup.+, 100%).
[5177] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.96 (br.s, 1H, --NH);
9.03 (s, 1H); 8.36 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.47 (d,
J=8.2, 1H, --NH); 7.44 (s, 1H); 7.33 (d, J=8.4, 1H); 7.06 (d,
J=8.4, 1H); 5.41 (t, J=5.6, 1H, --OH); 3.86 (d, J=6.8, 2H); 3.79
(d, J=5.6, 2H & m, 1H); 3.69 (m, 1H); 2.33 (s, 3H); 2.02 (m,
2H); 1.83 (m, 2H); 1.47 (m, 4H); 0.93 (m, 1H); 0.34 (m, 2H); 0.19
(m, 2H).
Example 244
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5178] Starting from
trans-4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A170) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound is
obtained as colorless solid.
[5179] MS (ESI): m/z=492 (MH.sup.+, 100%).
[5180] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 11.96 (br.s, 1H, --NH);
9.03 (s, 1H); 8.36 (d, J=7.9, 1H, --NH); 8.22 (s, 1H); 7.44 (d,
J=2.0, 1H); 7.42 (d, J=10.0, 1H, --NH); 7.33 (dd, J.sub.1=8.4,
J.sub.2=2.0, 1H); 7.06 (d, J=8.4, 1H); 5.41 (d, J=6.1, 1H, --OH);
3.96 (m, 1H); 3.86 (d, J=6.8, 2H & m, 1H); 3.64 (m, 1H); 2.32
(s, 3H); 2.03 (m, 2H); 1.81 (m, 2H); 1.44 (m, 4H); 1.21 (d, J=6.8,
3H); 0.93 (m, 1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 245
trans-4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
{4-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5181] Starting from
trans-4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A170) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
is obtained as colorless solid.
[5182] MS (ESI): m/z=504 (MH.sup.+, 100%).
[5183] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 11.95 (br.s, 1H, --NH);
9.03 (s, 1H); 8.36 (d, J=7.9, 1H, --NH); 8.22 (d, J=3.4, 1H); 7.57
(d, J=8.4, 1H, --NH); 7.44 (d, J=2.1, 1H); 7.33 (dd, J.sub.1=8.4,
J.sub.2=2.1, 1H); 7.06 (d, J=8.4, 1H); 6.20 (s, 1H, --OH); 3.86 (d,
J=6.9, 2H & m, 1H); 3.70 (m, 1H); 2.32 (s, 3H); 2.03 (m, 2H);
1.82 (m, 2H); 1.59-1.38 (m, 4H); 1.03 (m, 2H); 0.93 (m, 1H); 0.83
(m, 2H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 246
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-(2-hydroxy-acetyl)piperidin-4-yl]-amide
[5184] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A171) and acetic acid
chlorocarbonyl-methyl ester the title compound is obtained as
colorless solid.
[5185] MS (ESI): m/z=464 (MH.sup.+, 100%).
[5186] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.03 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.25 (s, 1H); 7.44 (d,
J=1.9, 1H); 7.33 (dd, J.sub.1=8.5, J.sub.2=1.9, 1H); 7.06 (d,
J=8.5, 1H); 4.51 (t, J=5.4, 1H, --OH); 4.23-4.11 (m, 2H); 4.14 (d,
J=5.4, 2H); 3.87 (d, J=6.9, 2H); 3.69 (m, 1H); 3.20 (m, 1H); 3.00
(m, 1H); 2.33 (s, 3H); 1.99 (m, 2H); 1.56 (m, 1H); 1.44 (m, 1H);
0.94 (m, 1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 247
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5187] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A171) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound is obtained as
colorless solid.
[5188] MS (ESI): m/z=478 (MH.sup.+, 100%).
[5189] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.03 (s, 1H); 8.52 (d, J=7.8, 1H, --NH); 8.25 (s, 1H); 7.44 (d,
J=1.9, 1H); 7.33 (dd, J.sub.1=8.5, J.sub.2=1.9, 1H); 7.06 (d,
J=8.5, 1H); 4.86 (d, J=6.9, 1H, --OH); 4.47 (m, 1H); 4.29-4.10 (m,
2H); 3.97 (m, 1H); 3.86 (d, J=6.8, 2H); 3.29 (m, 1H); 3.97 (m, 1H);
2.33 (s, 3H); 1.99 (m, 2H); 1.57 (m, 1H); 1.43 (m, 1H); 1.21 (br.s,
3H); 0.94 (m, 1H); 0.34 (m, 2H); 0.19 (m, 2H).
Example 248
4-(2-Cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide
[5190] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A171) and acetic acid
1-chlorocarbonyl-cyclopropyl ester the title compound is obtained
as colorless solid.
[5191] MS (ESI): m/z=490 (MH.sup.+, 100%).
[5192] .sup.1H-NMR 400 MHz, DMSO-d.sub.6): 11.99 (br.s, 1H, --NH);
9.03 (s, 1H); 8.53 (d, J=7.9, 1H, --NH); 8.25 (s, 1H); 7.44 (d,
J=1.9, 1H); 7.33 (dd, J.sub.1=8.5, J.sub.2=1.9, 1H); 7.06 (d,
J=8.5, 1H); 6.31 (s, 1H, --OH); 4.28 (m, 1H); 4.24-4.10 (m, 2H);
3.87 (d, J=6.9, 2H); 3.17 (m, 2H); 2.33 (s, 3H); 1.99 (m, 2H); 1.53
(m, 1H); 0.94 (m, 3H); 0.77 (m, 2H); 0.34 (m, 2H); 0.19 (m,
2H).
Example 249
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide
[5193] Starting from
4-(2-cyclopropylmethoxy-5-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid piperidin-4-ylamide (example A175) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound was obtained as
colorless solid.
[5194] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5195] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.15 (s, 1H, --NH);
9.02 (s, 1H); 8.45 (d, J=7.7, 1H, --NH); 8.29 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.86 (d, J=6.7, 1H,
--OH); 4.47 (m, 1H); 4.31-4.10 (m, 2H); 3.96 (qu, J=6.9, 2H &
m, 1H); 3.27 (m, 1H); 2.97 (m, 1H); 1.99 (m, 2H); 1.62-1.31 (m,
2H); 1.20 (br.s, 3H); 1.03 (t, J=6.9, 3H).
Example 250
4-(5-Ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide
[5196] Starting from
4-(5-ethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A176) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound was obtained as
colorless solid.
[5197] MS (ESI): m/z=468 (MH.sup.+, 100%).
[5198] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.72 (s, 1H, --NH);
9.01 (s, 0.5H); 8.99 (s, 0.5H); 8.57 (d, J=7.0, 1H, --NH); 8.31 (s,
1H); 7.02 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.90
(br.s, 1H, --OH); 4.60 (m, 0.5H); 4.53 (m, 0.5H); 4.33 (m, 0.5H);
4.27 (m, 0.5H); 3.95 (qu, J=6.9, 2H); 3.88-3.32 (m, 4H); 2.34-2.13
(m, 1H); 2.08 (m, 0.5H); 1.94 (m, 0.5H); 1.20 (m, 3H); 1.03 (t,
J=6.9, 3H).
Example 251
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5199] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid piperidin-4-ylamide (example A177) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound was obtained as
colorless solid.
[5200] MS (ESI): m/z=496 (MH.sup.+, 100%).
[5201] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.14 (s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.8, 1H, --NH); 8.28 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.86 (d, J=6.3, 1H,
--OH); 4.47 (m, 1H); 4.23 (m, 1H); 4.16 (m, 1H); 3.97 (m, 1H); 3.85
(t, J=6.4, 2H); 3.27 (m, 1H); 2.96 (m, 1H); 1.99 (m, 2H); 1.54 (m,
1H); 1.42 (m, 2H & m, 1H); 1.21 (br.s, 3H); 0.63 (t, J=7.4,
3H).
Example 252
4-(5-Propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide
[5202] Starting from
4-(5-propoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxy-
lic acid (R)-pyrrolidin-3-ylamide (example A178) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound was obtained as
colorless solid.
[5203] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5204] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.99 (s, 1H, --NH);
9.01 (s, 0.5H); 8.99 (s, 0.5H); 8.57 (d, J=6.9, 1H, --NH); 8.30 (s,
1H); 7.03 (d, J=8.6, 1H); 6.58 (d, J=8.6, 1H); 6.00 (s, 2H); 4.90
(br.s, 1H, --OH); 4.60 (m, 0.5H); 4.52 (m, 0.5H); 4.32 (m, 0.5H);
4.27 (m, 0.5H); 3.86 (t, J=6.4, 2H); 3.80-3.34 (m, 4H); 2.33-2.14
(m, 1H); 2.08 (m, 0.5H); 1.97 (m, 0.5H); 1.42 (m, 2H); 1.23 (d,
J=6.5, 1.5H); 1.20 (d, J=6.5, 1.5H); 0.62 (t, J=7.4, 3H).
Example 253
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide
[5205] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid piperidin-4-ylamide (example A179) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound was obtained as
colorless solid.
[5206] MS (ESI): m/z=510 (MH.sup.+, 100%).
[5207] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.24 (s, 1H, --NH);
9.02 (s, 1H); 8.44 (d, J=7.7, 1H, --NH); 8.28 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00 (s, 2H); 4.86 (d, J=6.9, 1H,
--OH); 4.47 (m, 1H); 4.23 (m, 1H); 4.16 (m, 1H); 3.97 (m, 1H); 3.88
(t, J=6.4, 2H); 3.27 (m, 1H); 2.96 (m, 1H); 1.99 (m, 2H); 1.54 (m,
1H); 1.42 (m, 2H & m, 1H); 1.21 (br.s, 3H); 0.99 (m, 2H); 0.69
(t, J=7.4, 3H).
Example 254
4-(5-Butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyli-
c acid [(R)-1-((S)-2-hydroxy-propionyl)-pyrrolidin-3-yl]amide
[5208] Starting from
4-(5-butoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxyl-
ic acid (R)-pyrrolidin-3-ylamide (example A181) and acetic acid
(S)-1-chlorocarbonyl-ethyl ester the title compound was obtained as
colorless solid.
[5209] MS (ESI): m/z=496 (MH.sup.+, 100%).
[5210] .sup.1H-NMR 300 MHz, DMSO-d.sub.6): 12.17 (br.s, 1H, --NH);
9.01 (s, 0.5H); 8.99 (s, 0.5H); 8.57 (d, J=7.0, 1H, --NH); 8.30 (s,
1H); 7.02 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.01 (s, 2H);
4.99-4.81 (m, 1H, --OH); 4.60 (m, 0.5H); 4.52 (m, 0.5H); 3.88 (t,
J=6.4, 2H); 3.84-3.33 (m, 4H); 2.33-2.12 (m, 1H); 2.06 (m, 0.5H);
1.96 (m, 0.5H); 1.39 (m, 2H); 1.23 (d, J=6.5, 1.5H); 1.20 (d,
J=6.5, 1.5H); 1.05 (m, 2H); 0.69 (t, J=7.4, 3H).
Example 255
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5211] Starting from
trans-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A182) and
acetic acid chlorocarbonyl-methyl ester the title compound was
obtained as colorless solid.
[5212] MS (ESI): m/z=498 (MH.sup.+).
[5213] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.00 (s, 1H); 8.39 (d, J=7.8, 1H, --NH); 8.22 (d, J=3.3, 1H); 7.69
(d, J=8.3, 1H); 7.48 (d, J=8.3, 1H, --NH); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 5.42 (t, J=5.7, 1H, --OH); 4.23 (t,
J=4.6, 2H); 3.88 (s, 3H); 3.78 (d, J=5.7, 2H & m, 1H); 3.68 (m,
1H); 3.54 (t, J=4.6, 2H); 3.13 (s, 3H); 2.01 (m, 2H); 1.82 (m, 2H);
1.44 (m, 4H).
Example 256
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5214] Starting from
trans-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A182) and
acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound was
obtained as colorless solid.
[5215] MS (ESI): m/z=512 (MH.sup.+).
[5216] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.00 (s, 1H); 8.39 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.69 (d,
J=8.3, 1H); 7.43 (d, J=8.3, 1H, --NH); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 5.43 (d, J=5.1, 1H, --OH); 4.23 (t,
J=4.6, 2H); 3.93 (m, 1H); 3.88 (s, 3H); 3.82 (m, 1H); 3.63 (m, 1H);
3.53 (t, J=4.6, 2H); 3.13 (s, 3H); 2.01 (m, 2H); 1.80 (m, 2H); 1.43
(m, 4H); 1.20 (d, J=6.7, 3H).
Example 257
trans-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
{-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5217] Starting from
trans-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidi-
ne-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A182) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
was obtained as colorless solid.
[5218] MS (ESI): m/z=524 (MH.sup.+).
[5219] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.72 (br.s, 1H, --NH);
9.00 (s, 1H); 8.39 (d, J=7.8, 1H, --NH); 8.22 (s, 1H); 7.69 (d,
J=8.5, 1H); 7.57 (d, J=8.5, 1H, --NH); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.5, J.sub.2=2.2, 1H); 6.20 (s, 1H, --OH); 4.23 (t, J=4.6,
2H); 3.87 (s, 3H); 3.84 (m, 1H); 3.68 (m, 1H); 3.54 (t, J=4.6, 2H);
3.13 (s, 3H); 2.01 (m, 2H); 1.82 (m, 2H); 1.48 (m, 4H); 1.01 (m,
2H); 0.81 (m, 2H).
Example 258
cis-4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine--
7-carboxylic acid
{-[(1-hydroxy-cyclopropanecarbonyl)-amino]-cyclohexyl}-amide
[5220] Starting from
cis-4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A183) and
acetic acid 1-chlorocarbonyl-cyclopropyl ester the title compound
was obtained as colorless solid.
[5221] MS (ESI): m/z=524 (MH.sup.+).
[5222] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.73 (br.s, 1H, --NH);
9.04 (s, 1H); 8.71 (d, J=7.8, 1H, --NH); 8.23 (s, 1H); 7.70 (d,
J=8.3, 1H); 7.56 (d, J=7.8, 1H, --NH); 6.77 (s, 1H); 6.76 (dd,
J.sub.1=8.3, J.sub.2=2.2, 1H); 6.25 (s, 1H, --OH); 4.24 (t, J=4.6,
2H); 4.08 (m, 1H); 3.88 (s, 3H); 3.78 (m, 1H); 3.55 (t, J=4.6, 2H);
3.14 (s, 3H); 1.85-1.67 (m, 8H); 1.82 (m, 2H); 1.03 (m, 2H); 0.83
(m, 2H).
Example 259
4-[4-Methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid
[1-(1-hydroxy-cyclopropanecarbonyl)-piperidin-4-yl]-amide
[5223] Starting from
4-[4-methoxy-2-(2-methoxy-ethoxy)-phenyl]-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid piperidin-4-ylamide (example A184) and acetic acid
1-chlorocarbonyl-cyclopropyl ester the title compound was obtained
as colorless solid.
[5224] MS (ESI): m/z=510 (MH.sup.+).
[5225] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.74 (br.s, 1H, --NH);
9.00 (s, 1H); 8.56 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.70 (d,
J=8.3, 1H); 6.77 (s, 1H); 6.76 (dd, J.sub.1=8.3, J.sub.2=2.1, 1H);
6.30 (s, 1H, --OH); 4.30 (m, 1H); 4.24 (t, J=4.6, 2H); 4.18 (m,
2H); 3.87 (s, 3H); 3.54 (t, J=4.6, 2H); 3.13 (s, 3H & m, 2H);
2.00 (m, 2H); 1.51 (m, 2H); 0.94 (m, 2H); 0.77 (m, 2H).
Example 260
trans-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5226] Starting from
trans-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyr-
imidine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A185)
and acetic acid chlorocarbonyl-methyl ester the title compound was
obtained as colorless solid.
[5227] MS (ESI): m/z=512 (MH.sup.+).
[5228] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.12 (br. s, 1H,
--NH); 9.02 (s, 1H); 8.33 (d, J=7.8, 1H, --NH); 8.23 (s, 1H); 7.47
(d, J=8.2, --NH); 7.02 (d, J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01
(s, 2H); 5.42 (br.s, 1H, --OH); 4.03 (t, J=4.7, 2H); 3.79 (s, 2H
& m, 2H); 3.39 (t, J=4.7, 2H); 3.02 (s, 3H); 2.04 (m, 2H); 1.81
(m, 2H); 1.45 (m, 4H).
Example 261
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[4-(2-hydroxy-acetylamino)-cyclohexyl]-amide
[5229] Starting from
cis-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A186)
and acetic acid chlorocarbonyl-methyl ester the title compound was
obtained as colorless solid.
[5230] MS (ESI): m/z=512 (MH.sup.+).
[5231] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.20 (br.s, 1H, --NH);
9.05 (s, 1H); 8.59 (d, J=7.5, 1H; --NH); 8.28 (s, 1H); 7.56 (d,
J=7.7, 1H, --NH); 7.03 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.02
(s, 2H); 5.40 (br.s, 1H, --OH); 4.04 (t, J=4.7, 2H & m, 1H);
3.82 (s, 2H & m, 1H); 3.39 (t, J=4.7, 2H); 3.03 (s, 3H); 1.72
(m. 8H).
Example 262
cis-4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[4-((S)-2-hydroxy-propionylamino)-cyclohexyl]-amide
[5232] Starting from
cis-4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid (4-amino-cyclohexyl)-amide (example A186)
and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title compound
was obtained as colorless solid.
[5233] MS (ESI): m/z=526 (MH.sup.+).
[5234] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 11.82 (br.s, 1H, --NH);
9.05 (s, 1H); 8.57 (d, J=7.4, 1H; --NH); 8.28 (s, 1H); 7.50 (d,
J=7.7, 1H, --NH); 7.03 (d, J=8.6, 1H); 6.62 (d, J=8.6, 1H); 6.02
(s, 2H); 5.37 (br.s, 1H, --OH); 4.04 (t, J=4.7, 2H & m, 1H);
3.99 (m, 1H); 3.76 (m, 1H); 3.39 (t, J=4.7, 2H); 3.03 (s, 3H); 1.74
(m. 8H); 1.22 (d, J=6.7, 3H).
Example 263
4-[5-(2-Methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5235] Starting from
4-[5-(2-methoxy-ethoxy)-benzo[1,3]dioxol-4-yl]-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid piperidin-4-ylamide (example A187) and acetic
acid (S)-1-chlorocarbonyl-ethyl ester the title compound was
obtained as colorless solid.
[5236] MS (ESI): m/z=512 (MH.sup.+).
[5237] .sup.1H-NMR (200 MHz, DMSO-d.sub.6): 12.19 (br.s, 1H, --NH);
9.02 (s, 1H); 8.45 (d, J=7.7, 1H; --NH); 8.30 (s, 1H); 7.02 (d,
J=8.6, 1H); 6.61 (d, J=8.6, 1H); 6.01 (s, 2H); 4.87 (d, J=6.9, 1H,
--OH); 4.47 (m, 1H); 4.18 (m, 2H); 4.03 (t, J=4.7, 2H); 3.92 (m,
1H); 3.39 (t, J=4.7, 2H); 3.30 (s, 1H); 3.02 (s, 3H); 2.94 (m, 1H);
1.99 (m, 2H); 1.51 (m, 2H); 1.21 (d, J=6.3, 3H).
Example 264
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-((S)-2-hydroxy-propanoyl)piperidin-4-yl]-amide
[5238] To a solution of
4-(5-acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid from example A81 (43 mg; 0.12 mmol) in
dichloromethane (2 mL) is added
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.16
mmol), triethylamine (0.24 mmol) and 1-hydroxybenzotriazole (0.12
mmol). The suspension is stirred for 20 min at ambient temperature
and then (S)-1-(4-amino-piperidin-1-yl)-2-hydroxy-propan-1-one
hydrochloride from example A190 (0.16 mmol) is added. The reaction
mixture is stirred overnight at ambient temperature. The volatiles
are evaporated and the crude is distributed between ethyl acetate
and aqueous phosphate buffer (1M, pH=7). The organic phase is
separated, washed with aqueous phosphate buffer and evaporated to
dryness. The obtained crude product is purified by preparative HPLC
yielding 38 mg of the title compound as white solid.
[5239] MS (ESI): m/z=506 (MH.sup.+, 100%).
[5240] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.15 (s, 1H, --NH),
9.10 (s, 1H), 8.52 (d, 1H, J=7 Hz, NH), 8.30 (s, 1H), 8.21 (d, 1H,
J=1.5 Hz), 8.12 (dd, 1H, J=9, 1.5 Hz), 7.28 (d, 1H, J=9 Hz), 4.45
(m, 1H), 4.18 (m, 2H), 4.02 (d, 2H, J=7 Hz), 3.28 (m, 1H), 2.98 (m,
1H), 2.60 (s, 3H), 1.98 (m, 2H), 1.50 (m, 2H), 1.20 (m, 3H), 1.00
(m, 1H), 0.35 (m, 2H), 0.24 (m, 2H).
[5241] The following compounds are obtained analogously to the
procedure described in above example 264.
Example 265
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid [1-(2-methoxy-acetyl)piperidin-4-yl]-amide
[5242] Starting from
4-(5-acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A81) and
1-(4-amino-piperidin-1-yl)-2-methoxy-ethanone (A192) the title
compound is obtained as colorless solid.
[5243] MS (ESI): m/z=506 (MH.sup.+, 100%).
[5244] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H, --NH);
9.10 (s, 1H); 8.50 (d, J=7.0, 1H, --NH); 8.32 (s, 1H); 8.20 (d,
J=1.5, 1H); 8.12 (dd, J.sub.1=9.0, J.sub.2=1.5, 1H); 7.25 (d,
J=9.0, 1H); 4.22 (m, 2H); 4.03 (m, 2H); 4.02 (d, J=7.0, 2H); 3.75
(m, 1H); 3.20 (m, 1H); 2.93 (m, 1H); 2.60 (s, 3H); 1.95 (m, 2H);
1.75 (m, 2H); 1.00 (m, 1H); 0.35 (m, 2H); 0.24 (m, 2H).
Example 266
4-(5-Acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-car-
boxylic acid (1-acetyl-piperidin-4-yl)-amide
[5245] Starting from
4-(5-acetyl-2-cyclopropylmethoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A81) and 1-(4-Amino-piperidin-1-yl)-ethanone
(A191) the title compound is obtained as colorless solid.
[5246] MS (ESI): m/z=476.0 (MH.sup.+, 100%).
[5247] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H, --NH);
9.10 (s, 1H); 8.52 (d, J=7.0, 1H); 8.32 (s, 1H); 8.20 (d, J=1.5,
1H); 8.12 (dd, J.sub.1=9.0, J.sub.2=1.5, 1H); 7.25 (d, J=9.0, 1H);
4.18 (m, 2H); 4.02 (d, J=7.0, 2H); 3.80 (m, 1H); 3.30 (m, 1H); 2.93
(m, 1H); 2.60 (s, 3H); 2.05 (s, 3H); 1.96 (m, 2H); 1.45 (m, 2H);
1.00 (m, 1H); 0.35 (m, 2H); 0.24 (m, 2H).
Example 267
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5248] Starting from
4-(5-acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (example A82) and
(S)-1-(4-amino-piperidin-1-yl)-2-hydroxy-propan-1-one;
hydrochloride (A190) the title compound is obtained as colorless
solid.
[5249] MS (ESI): m/z=520 (MH.sup.+, 100%).
[5250] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.10 (s, 1H, --NH);
9.08 (s, 1H); 8.52 (d, 1H, J=8.0, --NH); 8.30 (s, 1H); 8.13 (s,
1H); 7.10 (m, 1H); 4.87 (d, 1H, J=7.0, --OH); 4.45 (m, 1H); 4.20
(m, 2H); 4.02 (d, 2H, J=7.0); 3.98 (m, 1H); 3.30 (m, 1H); 3.00 (m,
1H); 2.60 (s, 3H); 2.55 (s, 3H); 1.98 (m, 2H); 1.40 (m, 2H); 1.23
(m, 3H): 1.00 (m, 1H); 0.35 (m, 2H); 0.24 (m, 2H).
Example 268
4-(5-Acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimid-
ine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[5251] Starting from
4-(5-acetyl-2-cyclopropylmethoxy-4-methyl-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (example A82) and
1-(4-amino-piperidin-1-yl)-ethanone (A191) the title compound is
obtained as colorless solid.
[5252] MS (ESI): m/z=490 (MH.sup.+, 100%).
[5253] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.10 (s, 1H, --NH);
9.05 (s, 1H); 8.36 (d, J=3.0, 1H); 8.10 (s, 1H); 7.10 (s, 1H); 4.00
(d, J=7.0, 2H); 2.60 (s, 3H); 2.55 (s, 3H); 1.00 (m, 1H); 0.37 (m,
2H); 0.24 (m, 2H).
Example 269
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide
[5254] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (example A67) and
trans-4-amino-cyclohexanecarboxylic acid (2-methoxy-ethyl)-amide
hydrochloride (A196) the title compound is obtained as colorless
solid.
[5255] MS (ESI): m/z=536 (MH.sup.+).
[5256] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.25 (br.s, 1H, --NH);
9.03 (s, 1H); 8.29 (d, J=7.8, 1H, --NH); 8.26 (s, 1H); 7.99 (t,
J=5.6, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 3.80 (m, 1H); 3.76 (d, J=6.8, 2H); 3.34 (m, 2H); 3.25 (s,
3H); 3.20 (m, 2H); 2.18 (m, 1H); 2.05 (m, 2H); 1.80 (m, 2H); 1.50
(m, 2H); 1.34 (m, 2H)); 0.87 (m, 1H); 0.29 (m, 2H); 0.10 (m,
2H).
Example 270
trans-4-(5-Cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyri-
midine-7-carboxylic acid
(4-cyclopropylcarbamoyl-cyclohexyl)-amide
[5257] Starting from
4-(5-cyclopropylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (example A67) and
trans-(4-cyclopropylcarbamoyl-cyclohexyl)-carbamic acid tart-butyl
ester (A195) the title compound is obtained as colorless solid.
[5258] MS (ESI): m/z=518 (MH.sup.+).
[5259] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.25 (br.s, 1H, --NH);
9.02 (s, 1H); 8.28 (d, J=7.9, 1H, --NH); 8.26 (s, 1H); 7.77 (d,
J=4.3, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.56 (d, J=8.6, 1H); 6.00
(s, 2H); 3.79 (m, 1H); 3.76 (d, J=6.7, 2H); 2.62 (m, 1H); 2.11-2.04
(m, 3H); 1.78 (m, 2H); 1.49 (m, 2H); 1.32 (m, 2H)); 0.87 (m, 1H);
0.59 (m, 2H); 0.38 (m, 2H); 0.29 (m, 2H); 0.10 (m, 2H).
Example 271
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide
[5260] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A73) and
trans-(4-cyclopropylcarbamoyl-cyclohexyl)-carbamic acid tert-butyl
ester (A195) the title compound is obtained as colorless solid.
[5261] MS (ESI): m/z=504 (MH.sup.+, 100%).
[5262] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.88 (br.s, 1H, --NH);
8.99 (s, 1H); 8.36 (d, J=7.9, 1H, --NH); 8.19 (s, 1H); 7.77 (d,
J=4.3, 1H, --NH); 7.61 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.2, 1H); 6.69 (d, J=2.2, 1H); 3.91 (d, J=6.9, 2H); 3.86
(s, 3H); 3.79 (m, 1H); 2.62 (m, 1H); 2.11-2.03 (m, 3H); 1.78 (m,
2H); 1.49 (m, 2H); 1.32 (m, 2H); 0.97 (m, 1H); 0.37 (m, 2H); 0.23
(m, 2H).
Example 272
trans-4-(2-Cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidin-
e-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide
[5263] Starting from
4-(2-cyclopropylmethoxy-4-methoxy-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-c-
arboxylic acid (example A73) and
trans-4-amino-cyclohexanecarboxylic acid (2-methoxy-ethyl)-amide
hydrochloride (A196) the title compound is obtained as colorless
solid.
[5264] MS (ESI): m/z=522 (MH.sup.+, 100%).
[5265] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 11.89 (br.s, 1H, --NH);
9.00 (s, 1H); 8.37 (d, J=7.9, 1H, --NH); 8.19 (s, 1H); 7.78 (t,
J=5.6, 1H, --NH); 7.61 (d, J=8.5, 1H); 6.72 (dd, J.sub.1=8.5,
J.sub.2=2.3, 1H); 6.69 (d, J=2.3, 1H); 3.92 (d, J=7.0, 2H); 3.86
(s, 3H); 3.80 (m, 1H); 3.34 (m, 2H); 3.25 (s, 3H); 3.20 (m, 2H);
2.18 (m, 1H); 2.05 (m, 2H); 1.80 (m, 2H); 1.50 (m, 2H); 1.33 (m,
2H); 0.97 (m, 1H); 0.36 (m, 2H); 0.23 (m, 2H).
Example 273
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (4-cyclopropylcarbamoyl-cyclohexyl)-amide
[5266] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A77) and
trans-(4-cyclopropylcarbamoyl-cyclohexyl)-carbamic acid tert-butyl
ester (A195) the title compound is obtained as colorless solid.
[5267] MS (ESI): m/z=492 (MH.sup.+, 100%).
[5268] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.08 (br.s, 1H, --NH);
9.05 (s, 1H); 8.32 (d, J=7.9, 1H, --NH); 8.28 (s, 1H); 7.77 (d,
J=4.3, 1H, --NH); 7.43 (dd, J.sub.1=8.9, J.sub.2=3.3, 1H); 7.38
(ddd, J1=J.sub.2=9.2, J.sub.3=3.3, 1H); 7.19 (dd, J1=9.2,
J.sub.2=4.4, 1H); 3.88 (d, J=6.9, 2H); 3.80 (m, 1H); 2.61 (m, 1H);
2.11-2.04 (m, 3H); 1.79 (m, 2H); 1.50 (m, 2H); 1.32 (m, 2H); 0.94
(m, 1H); 0.59 (m, 2H); 0.38 (m, 2H); 0.33 (m, 2H); 0.19 (m,
2H).
Example 274
trans-4-(2-Cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide
[5269] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-phenyl)-5H-pyrrolo[3,2-d]pyrimidine-7-ca-
rboxylic acid (example A77) and trans-4-amino-cyclohexanecarboxylic
acid (2-methoxy-ethyl)-amide hydrochloride (A196) the title
compound is obtained as colorless solid.
[5270] MS (ESI): m/z=510 (MH.sup.+, 100%).
[5271] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.08 (br.s, 1H, --NH);
9.06 (s, 1H); 8.33 (d, J=7.9, 1H, --NH); 8.28 (s, 1H); 7.79 (d,
J=5.5, 1H, --NH); 7.43 (dd, J.sub.1=9.0, J.sub.2=3.3, 1H); 7.38
(ddd, J.sub.1=J.sub.2=9.1, J.sub.3=3.3, 1H); 7.19 (dd, J.sub.1=9.1,
J.sub.2=4.4, 1H); 3.88 (d, J=6.9, 2H); 3.79 (m, 1H); 3.34 (m, 2H);
3.25 (s, 3H); 3.20 (m, 2H); 2.17 (m, 1H); 2.06 (m, 2H); 1.80 (m,
2H); 1.50 (m, 2H); 1.33 (m, 2H); 0.94 (m, 1H); 0.34 (m, 2H); 0.18
(m, 2H).
Example 275
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
[4-(2-methoxy-ethylcarbamoyl)-cyclohexyl]-amide
[5272] Starting
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A68) and
trans-4-amino-cyclohexanecarboxylic acid (2-methoxy-ethyl)-amide
hydrochloride (A196) the title compound is obtained as colorless
solid.
[5273] MS (ESI): m/z=550 (MH.sup.+, 100%).).
[5274] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.01 (s, 1H); 8.28 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.78 (t,
J=5.6, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00
(s, 2H); 3.84 (d, J=6.2, 1H); 3.79 (m, 1H); 3.33 (m, 2H); 3.25 (s,
3H); 3.20 (m, 2H); 2.36 (m, 1H); 2.17 (m, 2H); 2.05 (m, 2H); 1.80
(m, 2H); 1.68 (m, 3H); 1.57-1.44 (m, 5H); 1.33 (m, 2H).
Example 276
trans-4-(5-Cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid
(4-cyclopropylcarbamoyl-cyclohexyl)-amide
[5275] Starting from
4-(5-cyclobutylmethoxy-benzo[1,3]dioxol-4-yl)-5H-pyrrolo[3,2-d]pyrimidine-
-7-carboxylic acid (example A68) and
trans-(4-cyclopropylcarbamoyl-cyclohexyl)-carbamic acid tert-butyl
ester (A195) the title compound is obtained as colorless solid.
[5276] MS (ESI): m/z=532 (MH.sup.+, 100%).
[5277] .sup.1H-NMR (400 MHz, DMSO-d.sub.6): 12.28 (br.s, 1H, --NH);
9.01 (s, 1H); 8.27 (d, J=7.8, 1H, --NH); 8.24 (s, 1H); 7.77 (d,
J=4.3, 1H, --NH); 7.01 (d, J=8.6, 1H); 6.59 (d, J=8.6, 1H); 6.00
(s, 2H); 3.84 (d, J=6.2, 1H); 3.79 (m, 1H); 3.25 (s, 3H); 2.61 (m,
1H); 2.36 (m, 1H); 2.10-2.02 (m, 2H); 1.79 (m, 2H); 1.68 (m, 3H);
1.57-1.44 (m, 5H); 1.32 (m, 2H); 0.59 (m, 2H); 0.39 (m, 2H).
[5278] The following compounds are obtained analogously to the
procedure described in above example 1.
Example 277
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-acetyl-piperidin-4-yl)-amide
[5279] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A188) and acetyl chloride the title compound is obtained as
colorless solid
[5280] MS (ESI): m/z=468 (MH.sup.+, 100%).
[5281] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.90 (br.d, J=3.5, 1H,
--NH); 10.43 (s, 1H, --OH); 8.99 (s, 1H); 8.52 (d, J=7.9, 1H,
--NH); 8.29 (d, J=3.5, 1H); 7.45 (d, J=11.5, 1H); 6.70 (d, J=7.5,
1H); 4.27-4.06 (m, 2H); 3.81 (d, J=6.9, 2H); 3.80 (m, 1H); 3.27 (m,
1H); 2.92 (m, 1H); 2.04 (s, 3H); 1.96 (m, 2H); 1.55 (m, 1H); 1.39
(m, 1H); 0.96 (m, 1H); 0.35 (m, 2H); 0.22 (m, 2H).
Example 278
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid (1-propionyl-piperidin-4-yl)-amide
[5282] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A188) and propionyl chloride the title compound is obtained as
colorless solid
[5283] MS (ESI): m/z=482 (MH.sup.+, 100%).
[5284] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.90 (br.d, J=3.1, 1H,
--NH); 10.43 (br.s, 1H, --OH); 8.99 (s, 1H); 8.52 (d, J=7.8, 1H,
--NH); 8.25 (d, J=3.1, 1H); 7.44 (d, J=11.5, 1H); 6.70 (d, J=7.3,
1H); 4.23 (m, 1H); 4.13 (m, 1H); 3.83 (m, 1H); 3.81 (d, J=6.8, 2H);
3.24 (m, 1H); 2.93 (m, 1H); 2.36 (qu, J=7.3, 2H); 1.96 (m, 2H);
1.53 (m, 1H); 1.39 (m, 1H); 1.01 (t, J=7.3, 3H); 0.96 (m, 1H); 0.35
(m, 2H); 0.22 (m, 2H).
Example 279
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid
(1-acetyl-piperidin-4-yl)-amide
[5285] Starting from
4-[2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide
hydrochloride (example A189) and acetyl chloride the title compound
is obtained as colorless solid.
[5286] MS (ESI): m/z=518 (MH.sup.+, 100%).
[5287] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.05 (s, 1H); 8.48 (d, J=7.9, 1H, --NH); 8.35 (s, 1H); 7.64 (d,
J=10.8, 1H); 7.40 (t, J=73.2, 1H); 7.18 (d, J=6.8, 1H); 4.21 (m,
1H); 4.14 (m, 1H); 3.91 (d, J=6.9, 2H); 3.80 (m, 1H); 3.27 (m, 1H);
2.92 (m, 1H); 2.04 (s, 3H); 1.96 (m, 2H); 1.56 (m, 1H); 1.40 (m,
1H); 0.95 (m, 1H); 0.35 (m, 2H); 0.21 (m, 2H).
Example 280
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid
[1-(2-methoxy-ethanoyl)-piperidin-4-yl]amide
[5288] Starting from
4-[2-cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrr-
olo[3,2-d]pyrimidine-7-carboxylic acid piperidin-4-ylamide
hydrochloride (example A189) and methoxy-acetyl chloride the title
compound is obtained as colorless solid
[5289] MS (ESI): m/z=548 (MH.sup.+, 100%).
[5290] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.01 (br.s, 1H, --NH);
9.05 (s, 1H); 8.48 (d, J=7.9, 1H, --NH); 8.34 (s, 1H); 7.64 (d,
J=10.9, 1H); 7.41 (t, J=77.6, 1H); 7.18 (d, J=6.6, 1H); 4.16 (m,
2H); 4.12 (d J=2.6, 1H); 3.91 (d, J=7.1, 2H); 3.76 (m, 1H); 3.31
(s, 3H); 3.22 (m, 1H); 2.95 (m, 1H); 1.98 (m, 2H); 1.56 (m, 1H);
1.43 (m, 1H); 0.95 (m, 1H); 0.36 (m, 2H); 0.21 (m, 2H).
[5291] The following compounds are obtained analogously to the
procedure described in above example 171.
Example 281
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-(2-hydroxy-acetyl)piperidin-4-yl]-amide
[5292] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A188) and acetic acid chlorocarbonyl-methyl ester the title
compound is obtained as colorless solid
[5293] MS (ESI): m/z=484 (MH.sup.+, 100%).
[5294] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.91 (br.d, J=3.3, 1H,
--NH); 10.43 (br.s, 1H, --OH); 8.99 (s, 1H); 8.52 (d, J=7.7, 1H,
--NH); 8.25 (d, J=3.3, 1H); 7.44 (d, J=11.5, 1H); 6.70 (d, J=7.3,
1H); 4.51 (t, J=5.3, 1H, --OH); 4.28 (m, 2H); 4.13 (m, 2H); 3.81
(d, J=6.8, 2H); 3.69 (m, 1H); 3.19 (m, 1H); 3.00 (m, 1H); 1.97 (m,
2H); 1.56 (m, 1H); 1.42 (m, 1H); 0.96 (m, 1H); 0.35 (m, 2H); 0.22
(m, 2H).
Example 282
4-(2-Cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrimi-
dine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)piperidin-4-yl]-amide
[5295] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A188) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid
[5296] MS (ESI): m/z=498 (MH.sup.+, 100%).
[5297] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 11.99 (br.d, J=3.5, 1H,
--NH); 10.48 (br.s, 1H, --OH); 9.01 (s, 1H); 8.51 (d, J=7.7, 1H,
--NH); 8.29 (d, J=3.5, 1H); 7.54 (d, J=11.5, 1H); 6.71 (d, J=7.5,
1H); 4.46 (m, 1H); 4.32-3.87 (m, 4H); 3.82 (d, J=6.9, 2H); 3.27 (m,
1H); 2.97 (m, 1H); 1.98 (m, 2H); 1.55 (m, 1H); 1.42 (m, 1H); 1.21
(br.s, 3H); 0.96 (m, 1H); 0.35 (m, 2H); 0.22 (m, 2H).
Example 283
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid
[1-(2-hydroxy-acetyl)piperidin-4-yl]-amide
[5298] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A188) and acetic acid chlorocarbonyl-methyl ester the title
compound is obtained as colorless solid
[5299] MS (ESI): m/z=534 (MH.sup.+, 100%).
[5300] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.05 (s, 1H); 8.48 (d, J=7.9, 1H, --NH); 8.34 (d, J=3.5, 1H); 7.64
(d, J=10.9, 1H); 7.40 (t, J=73.2, 1H); 7.18 (d, J=6.6, 1H); 4.51
(br.s, 1H, --OH); 4.18 (m, 1H); 4.13 (m, 1H & d, J=4.6, 2H);
3.91 (d, J=7.1, 2H); 3.70 (m, 1H); 3.20 (m, 1H); 2.99 (m, 1H); 1.98
(m, 2H); 1.56 (m, 1H); 1.43 (m, 1H); 0.95 (m, 1H); 0.35 (m, 2H);
0.21 (m, 2H).
Example 284
4-[2-Cyclopropylmethoxy-4-(1,1-difluoro-methoxy)-5-fluoro-phenyl]-5H-pyrro-
lo[3,2-d]pyrimidine-7-carboxylic acid
[1-((S)-2-hydroxy-propionyl)-piperidin-4-yl]-amide
[5301] Starting from
4-(2-cyclopropylmethoxy-5-fluoro-4-hydroxy-phenyl)-5H-pyrrolo[3,2-d]pyrim-
idine-7-carboxylic acid piperidin-4-ylamide hydrochloride (example
A188) and acetic acid (S)-1-chlorocarbonyl-ethyl ester the title
compound is obtained as colorless solid
[5302] MS (ESI): m/z=548 (MH.sup.+, 100%).
[5303] .sup.1H-NMR (300 MHz, DMSO-d.sub.6): 12.16 (br.s, 1H, --NH);
9.06 (s, 1H); 8.49 (d, J=7.9, 1H, --NH); 8.34 (d, J=3.1, 1H); 7.65
(d, J=10.8, 1H); 7.41 (t, J=73.2, 1H); 7.18 (d, J=6.6, 1H); 4.87
(d, J=6.9, 1H, --OH); 4.47 (m, 1H); 4.23 (m, 1H); 4.17 (m, 1H) 3.95
(m, 1H); 3.91 (d, J=6.9, 2H); 3.26 (m, 1H); 2.97 (m, 1H); 1.99 (m,
2H); 1.56 (m, 1H); 1.44 (m, 1H); 1.22 (br.s, 3H); 0.94 (m, 1H);
0.35 (m, 2H); 0.21 (m, 2H).
Commercial Utility
[5304] The compounds of formula (I), the salts thereof, N-oxides of
the compounds and the salts thereof, and the stereoisomers of the
compounds, the salts, the N-oxides of the compounds and the
N-oxides of the salts thereof are hereinafter referred to as the
compounds of the invention. In particular, the compounds of the
invention are pharmaceutically acceptable.
[5305] The compounds of the invention have valuable pharmaceutical
properties which make them commercially utilizable. In particular,
as type 5 phosphodiesterase (PDE5) inhibitors, they are able to
influence the physiological and pathophysiological function of
various cells, e.g., but not limited to, smooth muscle cells,
fibroblasts, myofibroblasts and platelets, which are involved in a
great variety of physiological and pathophysiological mechanisms.
In particular, the PDE5 inhibiting compounds of the invention can
effect relaxation of the vasculature, thus increasing blood flow,
improve the spatial balance between blood perfusion and ventilation
within the lung ("re-matching" effect) thereby reducing the amount
of so-called low V/Q-areas [areas within the lung with high
perfusion (Q) but no or reduced ventilation (V)] and high V/Q-areas
(areas within the lung with low perfusion but high ventilation),
induce neurogenesis, inhibit platelet function, such as
aggregation, adhesion and mediator release and, thus, have an
anti-inflammatory effect. The compounds of the invention are
distinguished by valuable and desirable properties, such as, for
example, high efficacy, high selectivity, low toxicity, superior
bioavailability in general (e.g. good enteral absorption), superior
therapeutic window, superior pharmacokinetics (e.g. half-life),
absence of significant side effects, and further beneficial effects
related with their therapeutic and pharmaceutical suitability.
[5306] Accordingly, the invention further relates to the compounds
of the invention for the treatment or prophylaxis of diseases,
especially diseases alleviated by inhibition of the type 5
phospho-diesterase. In particular, the invention relates to the
compounds of the invention for the treatment or prophylaxis of the
following diseases:
male and female sexual dysfunction, such as, but not limited to,
male erectile dysfunction, premature ejaculation, Peyronie's
disease; acute and chronic airway diseases, such as, but not
limited to, COPD (chronic obstructive pulmonary disease),
bronchitis, emphysema, pulmonary vascular remodeling, pulmonary
hypertension, lung fibrosis, asthma, cystic fibrosis,
bronchiectasis, bronchiolitis obliterans, connective tissue
diseases, sarcoidosis, kyphoscoliosis, pneumoconiosis, amyotrophic
lateral sclerosis, thoracoplasty, extrinsic allergic alveolitis;
inflammatory diseases, such as, but not limited to, vasculature
inflammation, acute respiratory distress syndrome, mesangial
glomerulonephritis, chronic inflammatory bowel disease,
disseminated intravascular inflammation, allergic vasculitis,
dermatoses (e.g., but not limited to, psoriasis, toxic and allergic
contact eczema, atopic eczema, seborrhoeic eczema, Lichen simplex,
sunburn, pruritus in the anogenital area, alopecia greata,
hypertrophic scars, discoid lupus erythematosus, follicular and
widespread pyodermias, endogenous and exogenous acne, acne
rosacea), disorders of the arthritis type (e.g., but not limited
to, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis),
disorders of the immune system [e.g., but not limited to, AIDS
(acquired immunodeficiency syndrome), multiple sclerosis], graft
versus host reaction, allograft rejections, shock [e.g., but not
limited to, septic shock, endotoxin shock, gram-negative sepsis
shock, toxic shock syndrome and ARDS (adult respiratory distress
syndrome)], gastrointestinal inflammations (e.g., but not limited
to, Crohn's disease and ulcerative colitis); disorders which are
based on to allergic and/or chronic, immunological false reactions
(e.g., but not limited to, allergic rhinitis, allergic sinusitis,
chronic rhinitis, chronic sinusitis, allergic conjunctivitis, nasal
polyps); pain, such as, but not limited to, inflammatory pain;
right-heart failure, right heart hypertrophy (car pulmonale),
hypertension, hypercholesterolemia, hypertriglyceridemia; ischaemic
diseases, such as, but not limited to, diabetes mellitus, stroke,
coronary artery disease, angina (including, but not limited to,
vasospastic angina), myocardial infarction, peripheral artery
disease, cerebrovascular obstruction, sleep apnea, macular
ischaemia, arterial and venous occlusion, congestive heart failure;
diabetic gastroparesis and diseases with symptoms of gastroparesis;
diseases or conditions in which it is desirable to suppress
platelet function, for example, but not limited to, after stent
implantations (e.g., but not limited to, coronary stenting), after
bypass operations, in pulmonary hypertension, thrombotic diseases,
post-angioplasty stenosis, coronary artery disease, infarction
(e.g., but not limited to, myocardial infarction), instable angina
pectoris, stroke, and arterial and venous occlusion diseases (e.g.,
but not limited to, claudicatio intermittens); diseases or
conditions with an impairment or dysfunction of cerebral vascular
reactivity and/or neurovascular coupling, such as, but not limited
to, arteriosclerotic dementia, multi-infarct dementia, cerebral
senility; diseases which are based on neuronal damage or
degradation, such as but not limited to, stroke, spinal cord
injury, brain injury, morbus parkinson, amyotrophic lateral
sclerosis, morbus alzheimer, amyloidosis, prion diseases and
neuropathy; peripheral arterial diseases, chronic renal failure,
chronic heart failure, sepsis, senile dementia (Alzheimer's
disease), Creutzfeld-Jacob disease, septic encephalopathy,
arteriosclerotic encephalopathy, diabetes associated
encephalopathy, toxic encephalopathy, vascular and neuronal
dementia, Huntington's disease, Parkinson's disease, multiple
sclerosis and preeclampsia; portal hypertension, liver cirrhosis,
toxic liver damage (e.g., but not limited to, alcohol-induced liver
damage), hepatitis, thrombosis of the portal vein, Budd-Chiari
syndrome, malformation of liver veins, compression of liver veins
(e.g., but without limitation, due to tumors), arteriovenous
fistula, diseases associated with an enlarged spleen,
schistosomiasis (bilharziosis), sarcoidosis and other granulomatous
diseases, primary biliary cirrhosis, myeloproliferative disorders
(e.g., but not limited to, chronic myeloid leukemia,
osteomyelofibrosis), lymphatic systemic diseases, collagenosis
(e.g., but not limited to, systemic lupus erythematodes,
sclerodermia), morbus Osler (congenital arteriovenous
malformations, inter alia in the liver), nodular regenerative
hyperplasia, tricuspid insufficiency, pericarditis constrictive,
veno-occlusive disease (VOD), non-alcoholic steatohepatitis (NASH),
liver fibrosis; benign prostatic hyperplasia; insufficient
uteroplacental blood flow in pregnancies with fetal growth
restriction; insufficient brain skills, such as but not limited to,
verbal attainment, attention, concentration, deductive thinking,
central auditory processing, cognition, learning, vigilance,
apprehension and reagibility; Overactive Bladder; LUTS=lower
urinary tract symptoms; Raynauds syndrome/phenomenon.
[5307] In this respect, the term "pulmonary hypertension" in
particular embraces [5308] pulmonary arterial hypertension
including primary pulmonary hypertension (e.g. sporadic or
familial) and pulmonary arterial hypertension related, for example,
but without limitation, to collagen vascular disease, congenital
systemic-to-pulmonary shunts, portal hypertension, human
immunodeficiency virus infection, drugs or toxins (e.g., but not
limited to, anorexigens), persistent pulmonary hypertension of the
newborn; [5309] pulmonary venous hypertension due to, for example,
but without limitation, left-sided atrial or ventricular heart
disease, left-sided valvular heart disease, extrinsic compression
of central pulmonary veins (e.g. fibrosing mediastinitis,
adenopathy in relation to tumors), pulmonary veno-occlusive
disease; [5310] pulmonary hypertension associated with disorders of
the respiratory system or hypoxemia including, for example, but
without limitation, chronic obstructive pulmonary disease (COPD),
interstitial lung disease, sleep-disordered breathing, alveolar
hypoventilation disorders, chronic exposure to high altitude,
neonatal lung disease, alveolar-capillary dysplasia; [5311]
pulmonary hypertension caused by chronic thrombotic or embolic
diseases including thromboembolic obstruction of proximal pulmonary
arteries and obstruction of distal pulmonary arteries, such as
pulmonary embolism (due to thrombus, tumor, ova, parasites, or
foreign material), in situ thrombosis and sickle-cell disease, in
particular chronic thromboembolic pulmonary hypertension (CTEPH);
[5312] pulmonary hypertension caused by disorders directly
affecting the pulmonary vasculature including inflammatory
disorders (e.g., but not limited to, schistosomiasis, sarcoidosis)
and pulmonary capillary hemangiomatosis.
[5313] Preferably, the invention further relates to the compounds
of the invention for the treatment or prophylaxis of the following
diseases: acute and chronic airway diseases, such as pulmonary
hypertension, in particular chronic thromboembolic pulmonary
hypertension, lung fibrosis, asthma, bronchitis, emphysema and
chronic obstructive pulmonary disease.
[5314] The invention also relates to the use of a compound of the
invention in the manufacture of a pharmaceutical composition
inhibiting the type 5 phosphodiesterase, in particular a
pharmaceutical composition for the treatment or prophylaxis of
diseases alleviated by inhibition of the type 5 phosphodiesterase,
preferably, a pharmaceutical composition for the treatment or
prophylaxis of to the diseases exemplified above.
[5315] Preferably, the invention relates to the use of a compound
of the invention in the manufacture of a pharmaceutical composition
for the treatment or prophylaxis of an acute or chronic airway
disease, such as, but not limited to, pulmonary hypertension, lung
fibrosis, asthma, bronchitis, emphysema and chronic obstructive
pulmonary disease.
[5316] In a particularly preferred embodiment of the invention, the
invention relates to the use of a compound of the above examples in
the manufacture of a pharmaceutical composition for the treatment
or prophylaxis of an acute or chronic airway disease, such as, but
not limited to, pulmonary hypertension, lung fibrosis, asthma,
bronchitis, emphysema and chronic obstructive pulmonary
disease.
[5317] The invention further relates to a method of treating or
preventing a disease comprising administering to a patient in need
thereof a therapeutically effective amount of at least one of the
compounds of the invention.
[5318] In particular, the invention relates to a method of treating
or preventing one of the above mentioned diseases comprising
administering to a patient in need thereof a therapeutically
effective amount of at least one of the compounds of the
invention.
[5319] Especially, the invention relates to a method of treating or
preventing a disease which is alleviated by inhibition of the type
5 phosphodiesterase comprising administering to a patient in need
thereof a therapeutically effective amount of at least one of the
compounds of the invention.
[5320] Preferably, the invention relates to a method of treating or
preventing an acute or chronic airway disease, for example, but not
limited to, pulmonary hypertension, lung fibrosis, asthma,
bronchitis, emphysema and chronic obstructive pulmonary disease,
comprising administering to a patient in need thereof a
therapeutically effective amount of at least one of the compounds
of the invention.
[5321] In the above methods, the patient is preferably a mammal,
more preferably a human. Furthermore, in the above methods, at
least one of the compounds of the invention can be used.
Preferably, one or two of the compounds of the invention are used,
more preferably, one of the compounds of the invention is used.
[5322] In a particularly preferred embodiment of the invention, the
above methods of treating or preventing one of the above mentioned
diseases comprise administering to a patient in need thereof a
therapeutically effective amount of one compound of the examples
according to the present to invention.
[5323] The invention furthermore relates to a pharmaceutical
composition which comprises at least one of the compounds of the
invention together with at least one pharmaceutically acceptable
auxiliary.
[5324] The invention additionally relates to a pharmaceutical
composition for the treatment or prophylaxis of an acute or chronic
airway disease, in particular for the treatment or prophylaxis of
pulmonary hypertension, lung fibrosis, asthma, bronchitis,
emphysema and chronic obstructive pulmonary disease.
[5325] Preferably, the pharmaceutical composition comprises one or
two of the compounds of the invention. More preferably, the
pharmaceutical composition comprises one of the compounds of the
invention.
[5326] In a particularly preferred embodiment of the invention, the
pharmaceutical composition comprises a compound of the examples
according to the present invention together with at least one
pharmaceutically acceptable auxiliary.
[5327] The invention additionally relates to a pharmaceutical
composition comprising at least one of the compounds of the
invention, at least one pharmaceutically acceptable auxiliary and
at least one therapeutic agent selected from the group consisting
of corticosteroids, anticholinergics, beta-mimetics, lung
surfactants, endothelin antagonists, prostacyclins, calcium channel
blockers, beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides.
[5328] In this respect, the therapeutic agent includes the
corticosteroids, anticholinergics, beta-mimetics, lung surfactants,
endothelin antagonists, prostacyclins, calcium channel blockers,
beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides in form of the free compounds, the
pharmaceutically acceptable salts thereof, the pharmaceutically
acceptable derivatives thereof (e.g., but not limited to, ester
derivatives), the solvates thereof and the stereoisomers of the
compounds, salts, derivatives and solvates.
[5329] Examples of corticosteroids include without limitation
budesonide, fluticasone such as fluticasone propionate,
beclometasone such as beclometasone dipropionate, triamcinolone
such as triamcinolone acetonide, and ciclesonide. Examples of
anticholinergics include without limitation indacaterol, tiotropium
such as tiotropium bromide, and ipratropium such as ipratropium
bromide. Examples of beta-mimetics include without limitation
formoterol such as formoterol fumarate, and salmeterol such as
salmeterol xinafoate. Examples of lung surfactants include without
limitation lusupultide, poractant alfa, sinapultide, beractant,
bovactant, colfosceril such as colfosceril palmitate,
surfactant-TA, and calfactant. Examples of endothelin antagonists
include without limitation bosentan, ambrisentan and sitaxsentan
such as sitaxsentan sodium. Examples of prostacyclins include
without limitation iloprost such as iloprost tromethamine,
epoprostenol such as epoprostenol sodium and treprostinil such as
treprostinil sodium. Examples of calcium channel blockers include
without limitation amlodipine such as amlodipine besylate and
amlodipine maleate, nifedipine, diltiazem such as diltiazem
hydrochloride, verapamil such as verapamil hydrochloride, and
felodipine. Examples of beta-blockers include without limitation
bisoprolol such as bisoprolol fumarate, nebivolol, metoprolol such
as metoprolol succinate and metoprolol tartrate, carvedilol,
atenolol and nadolol. Examples of type 4 phosphodiesterase
inhibitors include without limitation roflumilast, roflumilast
N-oxide, cilomilast, tetomilast and oglemilast. Examples of
antidepressants include without limitation bupropion such as
bupropion hydrochloride. Examples of antibiotics include without
limitation amoxicillin, ampicillin, levofloxacin, clarithromycin,
ciprofloxacin such as ciprofloxacin hydrochloride, telithromycin
and azithromycin. Examples of anticoagulants include without
limitation clopidogrel, enoxaparin, cilostazol, nadroparin,
warfarin and abciximab. Examples of diuretics include without
limitation furosemide, bumetanide and torsemide. Examples of
digitalis glycosides include without limitation digoxin and
digitoxin.
[5330] In a preferred embodiment, the pharmaceutical composition
comprises a compound of the invention in combination with a
corticosteroid. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and budesonide, a compound of the
invention and fluticasone, a compound of the invention and
beclometasone, a compound of the invention and triamcinolone, or a
compound of the invention and ciclesonide.
[5331] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with an anticholinergic. In a particularly preferred embodiment,
the pharmaceutical composition comprises:
a compound of the invention and indacaterol, a compound of the
invention and tiotropium, or a compound of the invention and
ipratropium.
[5332] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a beta-mimetic. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and formoterol, or a compound of the
invention and salmeterol.
[5333] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the to invention in combination
with a lung surfactant. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and lusupultide, a compound of the
invention and poractant alfa, a compound of the invention and
sinapultide, a compound of the invention and beractant, a compound
of the invention and bovactant, a compound of the invention and
colfosceril, a compound of the invention and surfactant-TA, or a
compound of the invention and calfactant.
[5334] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with an endothelin antagonist. In a particularly preferred
embodiment, the pharmaceutical composition comprises:
a compound of the invention and bosentan, a compound of the
invention and ambrisentan, or a compound of the invention and
sitaxsentan.
[5335] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a prostacyclin. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and iloprost, a compound of the
invention and epoprostenol, a compound of the invention and
triprostinil.
[5336] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a calcium channel blocker. In a particularly preferred
embodiment, the pharmaceutical composition comprises:
a compound of the invention and amlodipine, a compound of the
invention and nifedipine, a compound of the invention and
diltiazem, a compound of the invention and verapamil, or a compound
of the invention and felodipine.
[5337] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a beta-blocker. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and bisoprolol, a compound of the
invention and nebivolol, a compound of the invention and
metoprolol, a compound of the invention and carvedilol, a compound
of the invention and atenolol, or a compound of the invention and
nadolol.
[5338] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a type 4 phosphodiesterase inhibitor. In a particularly
preferred embodiment, the pharmaceutical composition comprises:
a compound of the invention and roflumilast, a compound of the
invention and roflumilast N-oxide, a compound of the invention and
cilomilast, a compound of the invention and tetomilast, or a
compound of the invention and oglemilast.
[5339] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with an antidepressant. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and bupropion.
[5340] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with an antibiotic. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and amoxicillin, a compound of the
invention and ampicillin, a compound of the invention and
levofloxacin, a compound of the invention and clarithromycin, a
compound of the invention and ciprofloxacin, a compound of the
invention and telithromycin, or a compound of the invention and
azithromycin.
[5341] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with an anticoagulant. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and clopidogrel, a compound of the
invention and enoxaparin, a compound of the invention and
cilostazol, a compound of the invention and nadroparin, a compound
of the invention and warfarin, or a compound of the invention and
abciximab.
[5342] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a diuretic. In a particularly preferred embodiment, the
pharmaceutical composition comprises:
a compound of the invention and furosemide, a compound of the
invention and bumetanide, or a compound of the invention and
torsemide.
[5343] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a digitalis glycoside. In a particularly preferred embodiment,
the pharmaceutical composition comprises:
a compound of the invention and digoxin, or a compound of the
invention and digitoxin.
[5344] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a corticosteroid and a beta-mimetic. In a particularly
preferred embodiment, the pharmaceutical composition comprises:
a compound of the invention, budesonide and indacaterol, a compound
of the invention, budesonide and formoterol, a compound of the
invention, budesonide and salmeterol, a compound of the invention,
fluticasone and indacaterol, a compound of the invention,
fluticasone and formoterol, a compound of the invention,
fluticasone and salmeterol, a compound of the invention,
beclometasone and indacaterol, a compound of the invention,
beclometasone and formoterol, a compound of the invention,
beclometasone and salmeterol, a compound of the invention,
triamcinolone and indacaterol, a compound of the invention,
triamcinolone and formoterol, a compound of the invention,
triamcinolone and salmeterol, a compound of the invention,
ciclesonide and indacaterol, a compound of the invention,
ciclesonide and formoterol, or a compound of the invention,
ciclesonide and salmeterol.
[5345] In a further preferred embodiment, the pharmaceutical
composition comprises a compound of the invention in combination
with a corticosteroid and an anticholinergic. In a particularly
preferred embodiment, the pharmaceutical composition comprises:
a compound of the invention, budesonide and tiotropium, a compound
of the invention, budesonide and ipratropium, a compound of the
invention, fluticasone and tiotropium, a compound of the invention,
fluticasone and ipratropium, a compound of the invention,
beclometasone and tiotropium, a compound of the invention,
beclometasone and ipratropium, a compound of the invention,
triamcinolone and tiotropium, a compound of the invention,
triamcinolone and ipratropium, a compound of the invention,
ciclesonide and tiotropium, or a compound of the invention,
ciclesonide and ipratropium.
[5346] The above mentioned compound of the invention is preferably
a compound according to the examples.
[5347] The invention furthermore relates to pharmaceutical
compositions according to the invention, as defined above,
inhibiting the type 5 phosphodiesterase, especially for the
treatment or prophylaxis of diseases alleviated by inhibition of
type 5 phosphodiesterase, in particular for the treatment or
prophylaxis of the diseases exemplified above.
[5348] The invention also encompasses pharmaceutical compositions
according to the invention, as defined above, for the treatment or
prophylaxis of the following diseases: acute and chronic airway
diseases, such as pulmonary hypertension, lung fibrosis, asthma,
bronchitis, emphysema and chronic obstructive pulmonary
disease.
[5349] The pharmaceutical compositions according to the invention
preferably contain the compound or compounds of the invention in a
total amount of from 0.1 to 99.9 wt %, more preferably 5 to 95 wt
%, in particular 20 to 80 wt %. In case at least one therapeutic
agent selected from the group consisting of corticosteroids,
anticholinergics, beta-mimetics, lung surfactants, endothelin
antagonists, prostacyclins, calcium channel blockers,
beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides is present in the pharmaceutical compositions
of the invention, the total amount of said therapeutic agent or
therapeutic agents in the pharmaceutical compositions is preferably
in the range of from 0.1 to 99.9 wt %, more preferably 5 to 95 wt
%, in particular 20 to 80 wt %, under the provision that the total
amount of the compound or compounds of the invention and the
therapeutic agent or therapeutic agents is less than 100 wt %.
Preferably, the at least one compound of the invention and the at
least one therapeutic agent are present in the pharmaceutical
composition in a weight ratio of from 1000:1 to 1:1000, more
preferably 500:1 to 1:500.
[5350] As pharmaceutically acceptable auxiliaries, any auxiliaries
known to be suitable for preparing pharmaceutical compositions can
be used. Examples thereof include, but are not limited to,
solvents, excipients, dispersants, emulsifiers, solubilizers, gel
formers, ointment bases, antioxidants, preservatives, stabilizers,
carriers, fillers, binders, thickeners, complexing agents,
disintegrating agents, buffers, permeation promoters, polymers,
lubricants, coating agents, propellants, tonicity adjusting agents,
surfactants, colorants, flavorings, sweeteners and dyes. In
particular, auxiliaries of a type appropriate to the desired
formulation and the desired mode of administration are used.
[5351] The pharmaceutical compositions can be formulated, for
example, into tablets, coated tablets (dragees), pills, cachets,
capsules (caplets), granules, powders, suppositories, solutions
(e.g., but not limited to, sterile solutions), emulsions,
suspensions, ointments, creams, lotions, pastes, oils, to gels,
sprays and patches (e.g., but not limited to, transdermal
therapeutic systems). Additionally, the pharmaceutical compositions
can be prepared as e.g. liposome delivery systems, systems in which
the compound of the invention is coupled to monoclonal antibodies
and systems in which the compound of the invention is coupled to
polymers (e.g., but not limited to, soluble or biodegradable
polymers).
[5352] In case of pharmaceutical compositions comprising at least
one of the compounds of the invention and at least one therapeutic
agent selected from the group consisting of corticosteroids,
anticholinergics, beta-mimetics, lung surfactants, endothelin
antagonists, prostacyclins, calcium channel blockers,
beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides, the compound of the invention and the
therapeutic agent may be formulated together into the same dosage
form (e.g., but not limited to, tablets), separately into the same
dosage form (e.g., but not limited to, tablets), or into different
dosage forms (without limitation e.g. the compound of the invention
may be formulated as tablet and the therapeutic agent may be
formulated as powder, solution or suspension).
[5353] The pharmaceutical compositions can be manufactured in a
manner known to a person skilled in the art, e.g. by dissolving,
mixing, granulating, dragee-making, levigating, emulsifying,
encapsulating, entrapping or lyophilizing processes.
[5354] The selected formulation depends inter alia on the route of
administering the pharmaceutical composition. The pharmaceutical
compositions of the invention can be administered by any suitable
route, for example, by the oral, sublingual, buccal, intravenous,
intraarterial, intramuscular, subcutaneous, intracutaneous,
topical, transdermal, intranasal, intraocular, intraperitoneal,
intrasternal, intracoronary, transurethral, rectal or vaginal
route, by inhalation or by insufflation. Oral administration is
preferred.
[5355] In case of pharmaceutical compositions comprising at least
one of the compounds of the invention and at least one therapeutic
agent selected from the group consisting of corticosteroids,
anticholinergics, beta-mimetics, lung surfactants, endothelin
antagonists, prostacyclins, calcium channel blockers,
beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides, the compound of the invention and the
therapeutic agent may be administered by the same route, e.g.,
without limitation, orally, or by different routes, e.g., without
limitation, the compound of the invention can be administered
orally and the therapeutic agent can be administered by inhalation
or instillation.
[5356] Tablets, coated tablets (dragees), pills, cachets, capsules
(caplets), granules, solutions, emulsions and suspensions are e.g.
suitable for oral administration. In particular, said formulations
can be adapted so as to represent, for example, an enteric form, an
immediate release form, a delayed release form, a repeated dose
release form, a prolonged release form or a sustained release form.
Said forms can be obtained, for example, by coating tablets, by
dividing tablets into several compartments separated by layers
disintegrating under different conditions (e.g. pH conditions) or
by coupling the compound of the invention to a biodegradable
polymer.
[5357] Administration by inhalation or instillation is preferably
made by using an aerosol. The aerosol is a liquid-gaseous
dispersion, a solid-gaseous dispersion or a mixed
liquid/solid-gaseous dispersion.
[5358] The aerosol may be generated by means of aerosol-producing
devices such as dry powder inhalers (DPIs), pressurized metered
dose inhalers (PMDIs) and nebulizers. Depending on the kind of the
compound of the invention, and optionally the therapeutic agent, to
be administered, the aerosol-producing device can contain the
compound and, optionally, the therapeutic agent in form of a
powder, a solution or a dispersion. The powder may contain, for
example, one or more of the following auxiliaries: carriers,
stabilizers and fillers. The solution may contain in addition to
the solvent, for example, one or more of the following auxiliaries:
propellants, solubilizers (co-solvents), surfactants, stabilizers,
buffers, tonicity adjusting agents, preservatives and flavorings.
The dispersion may contain in addition to the dispersant, for
example, one or more of the following auxiliaries: propellants,
surfactants, stabilizers, buffers, preservatives and flavorings.
Examples of carriers include, but are not limited to, saccharides,
e.g. lactose and glucose. Examples of propellants include, but are
not limited to, fluorohydrocarbons, e.g. 1,1,1,2-tetrafluoroethane
and 1,1,1,2,3,3,3-heptafluoropropane.
[5359] The particle size of the aerosol particles (solid, liquid or
solid/liquid particles) is preferably less than 100 .mu.m, more
preferably it is in the range of from 0.5 to 10 .mu.m, in
particular in the range of from 2 to 6 .mu.m (D50 value, measured
by laser diffraction).
[5360] Specific aerosol-producing devices which may be used for
inhaled administration include, but are not limited to,
Cyclohaler.RTM., Diskhaler.RTM., Rotadisk.RTM., Turbohaler.RTM.,
Autohaler.RTM., Turbohaler.RTM., Novolizer.RTM., Easyhaler.RTM.,
Aerolizer.RTM., Jethaler.RTM., Diskus.RTM., Ultrahaler.RTM. and
Mystic.RTM. inhalers. The aerosol-producing devices may be combined
with spacers or expanders, e.g. Aerochamber.RTM., Nebulator.RTM.,
Volumatic.RTM. and Rondo.RTM., for improving inhalation
efficiency.
[5361] In case of topical administration, suitable pharmaceutical
formulations are, for example, ointments, creams, lotions, pastes,
gels, powders, solutions, emulsions, suspensions, oils, sprays and
patches (e.g., but not limited to, transdermal therapeutic
systems).
[5362] For parenteral modes of administration such as, for example,
intravenous, intraarterial, to intramuscular, subcutaneous,
intracutaneous, intraperitoneal and intrasternal administration,
preferably solutions (e.g., but not limited to, sterile solutions,
isotonic solutions) are used. They are preferably administered by
injection or infusion techniques.
[5363] In case of intranasal administration, for example, sprays
and solutions to be applied in drop form are preferred
formulations.
[5364] For intraocular administration, solutions to be applied in
drop form, gels and ointments are exemplified formulations.
[5365] Generally, the pharmaceutical compositions according to the
invention can be administered such that the dose of the compound of
the invention is in the range customary for type 5
phosphodiesterase inhibitors. In particular, a dose in the range of
from 0.01 to 4000 mg of the compound of the invention per day is
preferred. In this respect, it is to be noted that the dose is
dependent, for example, on the specific compound used, the species
treated, age, body weight, general health, sex and diet of the
subject treated, mode and time of administration, rate of
excretion, severity of the disease to be treated and drug
combination. In case the pharmaceutical composition of the
invention comprises at least one of the compounds of the invention
and at least one therapeutic agent selected from the group
consisting of corticosteroids, anticholinergics, beta-mimetics,
lung surfactants, endothelin antagonists, prostacyclins, calcium
channel blockers, beta-blockers, type 4 phosphodiesterase
inhibitors, antidepressants, antibiotics, anticoagulants, diuretics
and digitalis glycosides, the same dose ranges apply to the
therapeutic agent.
[5366] The pharmaceutical compositions according to the invention
can be administered in a single dose per day or in multiple
subdoses, for example, 2 to 4 doses per day. A single dose unit of
the pharmaceutical composition can contain e.g. from 0.01 mg to
4000 mg, preferably 0.1 mg to 2000 mg, more preferably 0.5 to 1000
mg, most preferably 1 to 500 mg, of the compound of the invention.
In case the pharmaceutical composition of the invention comprises
at least one of the compounds of the invention and at least one
therapeutic agent selected from the group consisting of
corticosteroids, anticholinergics, beta-mimetics, lung surfactants,
endothelin antagonists, prostacyclins, calcium channel blockers,
beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides, a single dose unit of the pharmaceutical
composition can contain e.g. from 0.01 mg to 4000 mg, preferably
0.1 mg to 2000 mg, more preferably 0.5 to 1000 mg, most preferably
1 to 500 mg, of the therapeutic agent.
[5367] Furthermore, the pharmaceutical composition can be adapted
to weekly, monthly or even more infrequent administration, for
example by using an implant, e.g. a subcutaneous or intramuscular
implant, by using the compound of the invention in form of a
sparingly soluble salt or by using the compound of the invention
coupled to a polymer. Administration of the pharmaceutical
composition in a single dose per day is preferred.
[5368] In case the pharmaceutical composition of the invention
comprises at least one of the compounds of the invention and at
least one therapeutic agent selected from the group consisting of
corticosteroids, anticholinergics, beta-mimetics, lung surfactants,
endothelin antagonists, prostacyclins, calcium channel blockers,
beta-blockers, type 4 phosphodiesterase inhibitors,
antidepressants, antibiotics, anticoagulants, diuretics and
digitalis glycosides, administration of the compound of the
invention and administration of the therapeutic agent can be made
simultaneously or sequentially. In case of sequential
administration, the compound of the invention can be administered
before or after administration of the therapeutic agent.
Biological Investigations
[5369] Method for measuring inhibition of the type 5
phosphodiesterase (PDE5) activity:
[5370] As a source for human PDE5, platelets are used. For that
purpose, 150 ml fresh blood from human donors anticoagulated with
citrate [final concentration 0.3% (w/v)] is centrifuged at 200 g
for 10 min to obtain the so-called platelet-rich-plasma (PRP) as a
supernatant. 1/10 volume of ACD solution (85 mM Na.sub.3-citrate,
111 mM D-glucose, 71 mM citric acid, pH 4.4) is added to 9/10
volume of PRP. After centrifugation (1,400 g, 10 min) the cell
pellet is resuspended in 3 ml homogenization buffer (NaCl 140 mM,
KCl 3.8 mM, EGTA (ethylene glycol tetraacetic acid) 1 mM,
MgCl.sub.2 1 mM, Tris-HCl 20 mM, beta-mercaptoethanol 1 mM, pH 8.2)
plus protease-inhibitor mix giving rise to the final concentrations
of 0.5 mM Pefablock (Roche), 10 .mu.M Leupeptin, 5 .mu.M
Trypsininhibitor, 2 mM Benzamidin and 10 .mu.M Pepstatin A. The
suspension is sonified and thereafter centrifuged for 15 min at
10,000 g. The resulting supernatant (platelet lysate) is used for
enzymatic testings.
[5371] PDE5A1 activity is inhibited by the compounds of the
invention in a modified SPA (scintillation proximity assay) test,
supplied by Amersham Biosciences (see procedural instructions
"phosphodiesterase [3H]cAMP SPA enzyme assay, code TRKQ 7090"),
carried out in 96-well microtitre plates (MTP's). The test volume
is 100 .mu.l and contains 20 mM Tris buffer (pH 7.4), 0.1 mg of BSA
(bovine serum albumin)/ml, 5 mM Mg.sup.2+, 1 .mu.M motapizone, 10
nM PDE2 inhibitor
2-(3,4-dimethoxybenzyl)-7-[(1R,2R)-2-hydroxy-1-(2-phenylethyl)propyl]-5-m-
ethylimidazo[5,1-f][1,2,4]triazin-4(3H)-one, 0.5 .mu.M cGMP (cyclic
guanosine monophosphate) (including about 50,000 cpm of [3H]cGMP as
a tracer), 1 .mu.l of the respective compound dilution in
dimethylsulfoxide (DMSO) and sufficient PDE5-containing platelet
lysat (10,000.times.g supernatant, see above) to ensure that 10-20
wt % of the cGMP is converted under the said experimental
conditions. The final concentration of DMSO in the assay (1% v/v)
does not substantially affect the activity of the PDE investigated.
After a preincubation of 5 min at 37.degree. C., the reaction is
started by adding the substrate (cGMP) and the assay is incubated
for a further 15 min; after that, it is stopped by adding SPA beads
(50 .mu.l). In accordance with the manufacturer's instructions, the
SPA beads had previously been resuspended in water, but are then
diluted 1:3 (v/v) in water; the diluted solution also contains 3 mM
8-methoxymethyl-3-isobutyl-1-methylxanthine (IBMX) to ensure a
complete PDE activity stop. After the beads have been sedimented
(>30 min), the MTP's are analyzed in commercially available
luminescence detection de-vices. The corresponding IC.sub.50 values
of the compounds for the inhibition of PDE activity are deter-mined
from the concentration-effect curves by means of non-linear
regression.
[5372] Representative inhibitory values determined for the
compounds of the invention are given in the following table:
TABLE-US-00001 Example -log IC.sub.50 (mol/l) 1 10.11 2 10.01 3
9.40 4 9.79 5 9.91 6 10.07 7 9.67 8 9.65 9 8.94 10 9.70 11 9.84 12
10.16 13 9.11 14 8.86 15 9.00 16 9.41 17 9.47 18 8.74 19 8.61 20
9.27 21 8.74 22 9.31 23 9.35 24 9.52 25 9.62 26 9.34 27 9.43 28
9.16 29 9.56 30 9.32 31 9.65 32 8.96 33 8.82 34 9.46 35 9.15 36
9.31 37 9.04 38 9.40 39 9.11 40 9.37 41 9.05 42 9.72 43 9.55 44
9.10 45 8.81 46 8.86 47 9.64 48 9.37 49 9.47 50 9.85 51 9.31 52
9.52 53 9.43 54 9.38 55 9.43 56 9.55 57 9.33 58 9.47 59 9.13 60
9.58 61 9.28 62 9.51 63 9.04 64 9.22 65 8.94 66 9.20 67 8.86 68
9.04 69 8.75 70 8.97 71 8.87 72 9.36 73 8.73 74 9.26 75 8.80 76
8.62 77 8.67 78 8.64 79 8.81 80 8.85 81 8.83 82 8.96 83 8.29 84
8.53 85 8.80 86 8.40 87 8.95 88 8.78 89 8.89 90 8.25 91 8.20 92
8.47 93 8.60 94 8.06 95 8.48 96 8.67 97 9.93 98 9.66 99 9.75 100
9.90 101 9.79 102 9.94 103 9.33 104 9.63 105 9.43 106 9.05 107 9.27
108 9.18 109 9.16 110 9.67 111 9.98 112 9.86 113 9.70 114 8.65 115
8.42 116 8.51 117 8.96 118 9.30 119 8.92 120 8.92 121 8.75 122 8.86
123 8.74 124 8.66 125 8.93 126 9.33 128 9.68 129 9.41 130 9.90 131
9.31 132 9.53 133 9.20 134 9.46 135 8.70 136 8.43 137 8.65 138 8.22
139 9.69 140 9.83 141 9.03 142 9.21 143 8.82 144 9.94 145 10.00 146
9.64 147 9.62 148 9.39 149 9.53 150 9.41 151 9.53 152 7.84 153 8.21
154 7.77 155 8.02 156 8.18 157 7.81 158 7.62 159 8.22 160 7.63 161
8.28 162 7.96 164 8.11 165 8.23 166 7.99 167 8.28 168 8.10 169 8.76
170 7.86 171 9.52 172 9.95 173 9.73 174 9.41 175 9.61 176 9.61 177
9.91 178 9.64 179 9.74 180 8.92 181 9.23 182 9.32 183 8.73 184 8.50
185 8.69 186 9.26 187 9.34 188 9.29 189 9.41 190 9.60 191 8.99 192
9.08 193 8.97 194 9.08 195 8.88 196 9.12 197 9.07 198 9.21 199 9.23
200 9.32 201 9.39 202 9.13 203 9.41 204 9.59 205 9.08 206 9.18 207
9.61 208 8.73 209 9.16 210 9.19 211 8.63 212 8.97 213 9.26 214 8.58
215 8.59 216 8.82 217 8.65 218 8.60 219 8.70 220 8.13 221 8.19 222
8.72 223 8.46 224 8.16 225 8.15 226 8.47 227 7.85 228 9.79 229 9.70
230 9.62 231 9.16 232 9.45 233 9.12 234 9.01 235 9.34 236 8.78 237
9.21 238 9.50 239 8.60 240 9.30 241 8.87 242 9.01 243 8.64 244 8.71
245 8.94 246 8.44 247 8.63 248 8.96
249 8.67 250 8.32 251 9.44 252 8.92 253 9.77 254 9.23 255 7.87 256
7.92 257 8.03 258 8.20 259 8.07 260 8.32 261 7.96 262 8.03 263 8.00
264 9.66 265 9.54 266 10.10 267 9.49 268 9.10 269 9.24 270 9.72 271
9.26 272 9.15 273 8.66 274 8.28 275 9.46 276 9.78 277 7.03 278 7.24
279 8.63 280 8.76 281 6.07 282 6.60 283 8.29 284 8.54
Animal Pharmacological Testing
[5373] Nitric oxide regulates smooth muscle tone by elevation of
cGMP via activation of guanylate cyclase and subsequent activation
of cyclic GMP-dependent protein kinase. The amplitude and duration
of the cGMP signal in smooth muscle is largely regulated by
cGMP-specific cyclic nucleotide phos-phodiesterase 5 (PDE5).
Therefore, inhibition of PDE5 or activation of guanylate cyclase
causes altered arterial blood pressure response, which is more
pronounced under conditions of acute arterial hypertension, which
can be easily induced by continuous intravenous (i.v.)
phenylephrine (PE)-infusion. The aim of the study was to evaluate
the effects of the selective PDE5 inhibitors described in this
invention on phenylephrine-induced acute arterial hypertension and
sodium-nitroprusside (SNP) induced blood pressure response in
anaesthetised male Sprague Dawley rats.
Method
[5374] The test compound (suspended in a 4% w/v aqueous
methylcellulose solution either 3 or 10 mg/kg) or placebo (i.e. 4%
aqueous methylcellulose solution) is administered orally to
conscious Sprague Dawley rats 90 min prior to SNP administration.
40 min later, rats are anaesthetised by intramuscular
administration of 80 mg/kg ketamine-HCl+4 mg/kg xylazin-HCl and
ventilated with .about.1.5% isoflurane in a mixture of ambient air
and 40% oxygen. Catheters for i.v. PE- and SNP-administration and
recording of mean arterial blood pressure (MAP) are inserted. One
hour after compound or placebo administration, a continuous i.v.
(V. femoralis) PE-infusion (3 .mu.g/kg/min at an infusion rate of
0.06 ml/min) is started and maintained till the end of the
experiment. 30 min after start of the PE-infusion, an i.v.-bolus of
the NO-donor sodium nitroprusside (SNP, 30 .mu.g/kg at a volume of
1.0 ml/kg) is administered. To assess the effect of test compounds
(PDE5 inhibitory activity) in comparison to placebo, MAP response
is analysed. MAP prior to SNP-administration and area under the
curve of MAP within 180 s following SNP-administration, corrected
for initial MAP (corr. AUC.sub.MAP 0-180s) is used, to describe
altered arterial vascular response and thus in vivo PDE5-inhibitory
activity. The efficacy (% change vs. control) achievable in this
model is approximately between -13% and -45% effect for the
examples 2, 3, 4, 6, 7, 8, 10, 11, 15, 16, 23, 24, 26, 50, 98, 99,
112, 113, 132, 171, 172, 173, 176, 177, 178, 179, 181, 182, 187,
228, 237, 269 and 272.
* * * * *